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Papers by raffaele maletta

Research paper thumbnail of Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Research paper thumbnail of Epidemiology and genetics of frontotemporal dementia: a door-to-door survey in Southern Italy

Neurobiology of Aging, Dec 1, 2012

Objectives-To estimate FTD prevalence, identify FTD-related mutations, correlate FTD phenotype wi... more Objectives-To estimate FTD prevalence, identify FTD-related mutations, correlate FTD phenotype with mutations in a Southern Italian population. Methods-Study population consisting of subjects ≥50 years of age residing in the Community of Biv. on January 1, 2004. Door-to-door two-phase design. Genetic and biochemical analyses were done on samples collected from 32 patients. Results-Prevalence rates were 0.6 for AD, 0.4 for VD, 3.5 for FTD, 0.2 for Parkinson Dementia and 1.2 for unspecified dementia. Three GRN (one known and two novel) mutations with reduced plasma protein levels were found associated to three distinct phenotypes (behavioural, affective and delirious type).

Research paper thumbnail of Genetic variation in APOE, GRN, and TP53 are phenotype modifiers in frontotemporal dementia

Neurobiology of Aging, Mar 1, 2021

Frontotemporal dementia (FTD) is a clinical, genetic, and pathologic heterogeneous group of neuro... more Frontotemporal dementia (FTD) is a clinical, genetic, and pathologic heterogeneous group of neurodegenerative diseases. In this study, we investigated the role of APOƐ4, rs5848 in GRN, and rs1042522 in TP53 gene as disease risk factors and/or phenotype modifiers in 440 FTD patients, including 175 C9orf72 expansion carriers. We found that the C9orf72 expansion carriers showing an earlier age at onset (p < 0.001). Among the clinical groups, the FTD-MND (motoneuron disease) showed the lowest survival (hazard ratio [HR] ¼ 4.12), and the progressive nonfluent aphasia group showed the highest onset age (p ¼ 0.03). In our cohort, the rs1042522 in TP53 was associated with disease onset (p ¼ 0.02) and survival (HR ¼ 1.73) and rs5848 GRN with a significantly shorter survival in CC homozygous patients (HR ¼ 1.98). The frequency of APOƐ4 carriers was significantly increased in the C9orf72 noncarriers (p ¼ 0.022). Although validation of our findings is necessary, our results suggest that TP53, GRN, and APOE genes may act as phenotype modifiers in FTD and should be considered in future clinical trials.

Research paper thumbnail of P3-404: Presenilins mutations are frequent in early-onset familial frontotemporal dementia

Alzheimers & Dementia, Jul 1, 2006

... Raffaele Maletta1 email address , Rosanna Colao1, Sabrina Anna Maria Curcio1, Francesca Frang... more ... Raffaele Maletta1 email address , Rosanna Colao1, Sabrina Anna Maria Curcio1, Francesca Frangipane1, Maria Mirabelli1, Gianfranco Puccio1, Maria Anfossi1, Livia Bernardi1, Angela Costanzo1, Francesca Ferrise1, Maura Gallo1,.

Research paper thumbnail of Neurodegenerative clinical records analyzer: detection of recurrent patterns within clinical records towards the identification of typical signs of neurodegenerative disease history

JLIS.it, May 15, 2023

Neurodegenerative clinical records analyzer: detection of recurrent patterns within clinical reco... more Neurodegenerative clinical records analyzer: detection of recurrent patterns within clinical records towards the identification of typical signs of neurodegenerative disease history* Erika Pasceri (a) , Mérième Bouhandi (b) , Claudia Lanza (c) , Anna Perri (d) , Valentina Laganà (e) , Raffaele Maletta (f) , Raffaele Di Lorenzo (g) , Amalia C. Bruni (h)

Research paper thumbnail of Nicastrin gene in familial and sporadic Alzheimer's disease

Neuroscience Letters, Dec 1, 2003

Nicastrin is a protein recently discovered associated to presenilins and involved in the producti... more Nicastrin is a protein recently discovered associated to presenilins and involved in the production of amyloid beta peptide that accumulates in Alzheimer's disease (AD) brain. In this study the nicastrin gene was examined for unknown mutations and polymorphisms in 104 patients with familial AD (52 early-onset and 52 late-onset), 174 sporadic AD and 191 healthy neurological controls of Italian origin. The scanning of the nicastrin gene identified a missense mutation (N417Y) in two patients with sporadic AD, in an early-onset familial AD and in a young control subject. Furthermore, we found two silent mutations and four intronic polymorphisms, three of them co-segregating in a single haplotype. We found some differences in the distribution of genotype alterations in the AD population compared to the controls. However, our data together with other evidence did not support the pathological role of missense mutation N417Y.

Research paper thumbnail of AβPP A713T Mutation in Late Onset Alzheimer's Disease with Cerebrovascular Lesions

Journal of Alzheimer's Disease, Jun 5, 2009

Mutations in the amyloid-beta protein precursor (AbetaPP) gene can cause autosomal dominant early... more Mutations in the amyloid-beta protein precursor (AbetaPP) gene can cause autosomal dominant early-onset Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease, or Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) associated with cerebral amyloid angiopathy (CAA), cerebral hemorrhage, or both. We have previously reported that the AbetaPP A713T mutation is associated with AD and subcortical ischemic lesions at magnetic resonance imaging in a large family which neuropathology confirmed CAA, stroke, and AD lesions. The objective of this clinical and molecular study was to investigate AbetaPP gene mutations in 59 patients affected by AD with cerebrovascular lesions (CVLs) and a family history of dementia. We identified three affected subjects with the AbetaPP A713T mutation. Since the prevalence of this mutation worldwide is very low, a common founder could exist in southern Italy. The pathogenicity of this mutation was confirmed and the clinical AD phenotype with CVLs seems to be a distinctive feature in the southern Italian population. The identification of these patients suggests that genetic epidemiology in large cohorts of familial late onset AD with CVLs would increase the probability of identifying AbetaPP mutations.

Research paper thumbnail of A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene

Neurology, Sep 13, 2004

Three members of an Italian family with autosomal dominant dementia and multiple strokes had the ... more Three members of an Italian family with autosomal dominant dementia and multiple strokes had the A713T mutation of the APP gene. The neuropathologic examination of the proband disclosed Alzheimer disease (AD) with severe cerebral amyloid angiopathy and multiple infarcts. This indicates that the A713T mutation of the APP gene, lying at the ␥-secretase cleavage site, can be responsible for AD with symptomatic cerebral amyloid angiopathy.

Research paper thumbnail of P3-166: Epidemiology of Frontotemporal dementia in southern Italy

Alzheimers & Dementia, Jul 1, 2009

... Francesca Frangipane; Rosanna Colao; Gianfranco Puccio; Sabrina AM Curcio; Maria Mirabelli; R... more ... Francesca Frangipane; Rosanna Colao; Gianfranco Puccio; Sabrina AM Curcio; Maria Mirabelli; Raffaele Maletta; Maria Anfossi; Livia Bernardi; Maura Gallo; Silvana Geracitano; Carmine Tomaino; Maria G. Muraca; Alessandra Clodomiro; Raffaele Di Lorenzo; Francesco ...

Research paper thumbnail of Circulating Levels of Soluble Receptor for Advanced Glycation End Products in Alzheimer Disease and Vascular Dementia

Archives of neurology, Nov 1, 2005

Background: The receptor for advanced glycation end products (RAGE) is a cell surface receptor th... more Background: The receptor for advanced glycation end products (RAGE) is a cell surface receptor that has been implicated in vascular disease and neurodegeneration. Low levels of its secreted isoform, soluble RAGE (sRAGE), have been regarded as a putative risk factor for atherosclerosis. In addition, administration of sRAGE has been shown to reduce development of cerebral ␤-amyloidosis in an Alzheimer disease mouse model. Objective: To investigate the role of sRAGE as a biological marker for Alzheimer disease and vascular dementia. Design: Cross-sectional study of 152 patients with a clinical diagnosis of Alzheimer disease, 91 with vascular dementia and 161 control subjects. Main Outcome Measure: Plasma levels of sRAGE. Results: Levels of sRAGE were significantly reduced in the plasma of patients with Alzheimer disease compared with that for those with either vascular dementia (PϽ.05) or with controls (PϽ.001). Conclusions: Patients with Alzheimer disease have reduced levels of sRAGE in plasma compared with patients with vascular dementia and controls. The striking reduction of circulating sRAGE in Alzheimer disease further supports a role for the RAGE axis in this clinical entity and requires further investigation.

Research paper thumbnail of Using the Theory of Planned Behavior and Past Behavior to Explain the Intention to Receive a Seasonal Influenza Vaccine among Family Caregivers of People with Dementia

International journal of translational medicine, May 19, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of P1-303: Low levels of sRAGE plasma concentration in different types of dementia

Alzheimers & Dementia, Jul 1, 2006

Background: Late-onset Alzheimer's disease is a complex neurodegenerative disorder characterized ... more Background: Late-onset Alzheimer's disease is a complex neurodegenerative disorder characterized by cognitive decline and distinct neuropathology. Multiple genes will be linked/associated with the disease. While case/control association studies are informative in the identification of risk factors, large extended pedigrees may be more useful in identifying genetic variants linked with the disease. Objective: To identify the mutations in the candidate genes linked with the disease in our large extended pedigrees. Methods: Our family 28 has 14 siblings, 5 affected with late-onset Alzheimer's disease and two of the father's siblings also affected with the disease. We have DNA on all of the siblings, including the five affected siblings, on the two affected of the father's siblings, on one of the mother's unaffected siblings, on many children and spouses, for a total of 63 samples. The clinical diagnosis was made according to the NINCDS-ADRDA criteria. In addition, we included an MRI of the brain, showing cortical atrophy with no evidence of strokes or tumors. Using a microsatellite scan of the DNA, we identified a location on chromosome 12 with a significant LOD score that was linked with the disease in family 28. Since the location was large containing many genes, we used the 100 K SNP microarrays for further analysis. We have identified several locations on chromosome 12 as well as locations on two other chromosomes that are associated with the disease. We are in the process of analyzing additional tag SNPs and microsatellites in candidate genes, before we begin resequencing to identify the genetic variations linked with the disease in this family. Conclusions: The use of extended pedigrees with multiple affected members may be more useful in identifying genetic variants linked with complex diseases.

Research paper thumbnail of A Clinical, Pathological And Molecular Study Of A Frontotemporal Dementia Sporadic Case

Research paper thumbnail of P1-319: Presenilin 2 Ser130Leu mutation in a case of late-onset “sporadic” AD

Alzheimers & Dementia, Jul 1, 2006

way ANOVA. Results: 78% of the AD cases were ApoE 4/3 (50%) or 4/4 (28%), while 32% were 3/3. Apo... more way ANOVA. Results: 78% of the AD cases were ApoE 4/3 (50%) or 4/4 (28%), while 32% were 3/3. ApoE 4/4 carriers had a younger age at onset (66Ϯ5 years, mean Ϯ SD) than 3/4 (69Ϯ7) and 3/3 carriers (71Ϯ6) but without statistical difference. The distribution of Apo E concordant sibpairs (nϭ22) was the following: 3/3 (nϭ4 sib-pairs, differences in age at onset 7.2Ϯ6.4 years), 3/4 (nϭ11, 4.5Ϯ3.0 years), 4/4 (nϭ7, 6.5Ϯ3.4 years). ApoE discordant sib-pairs (nϭ12) were the following: 3/4 versus 4/4 (nϭ8 sib-pairs, differences in age at onset 4.2Ϯ2.4 years), and 3/3 versus 3/4 (nϭ4, 5.5Ϯ1.9 years). Differences in age at onset in concordant ApoE sib-pairs (5.7Ϯ3.9 years) were not significantly different than in discordant sib-pairs (4.6Ϯ2.3 years). The presence of an extra ApoE allele in discordant sib-pairs only meant a younger age at onset in half of the pairs. Conclusions: Within sib-pairs with familial AD, ApoE genotype is not a major factor influencing age at onset. Other variables should be considered to influence the great variability in age at onset among affected siblings.

Research paper thumbnail of The Nerve Growth Factor Receptor (NGFR/P75<sup>ntr</sup>): A Major Player in Alzheimer’s Disease

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of The Shortening of Leukocyte Telomere Length Contributes to Alzheimer’s Disease: Further Evidence from Late-Onset Familial and Sporadic Cases

Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stabili... more Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are considered markers of premature cellular senescence. This is believed to contribute to age-related diseases, including Alzheimer's disease (AD) and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case-control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, which were all from Calabria, a region from south Italy. Following regression analysis, telomeres were found to be significantl...

Research paper thumbnail of Thymic function and survival at advance ages in nursing home residents from Southern Italy

Immunity & Ageing

Background Immunosenescence is a complex process characterized by an age-related remodelling of i... more Background Immunosenescence is a complex process characterized by an age-related remodelling of immune system. The prominent effects of the immunosenescence process is the thymic involution and, consequently, the decreased numbers and functions of T cells. Since thymic involution results in a collapse of the T-cell receptor (TCR) repertoire, a reliable biomarker of its activity is represented by the quantification of signal joint T-cell receptor rearrangement excision circles (sjTRECs) levels. Although it is reasonable to think that thymic function could play a crucial role on elderly survival, only a few studies investigated the relationship between an accurate measurement of human thymic function and survival at old ages. Methods and findings By quantifying the amount sjTRECs by real-time polymerase chain reaction (PCR), the decrease in thymic output in 241 nursing home residents from Calabria (Southern Italy) was evaluated to investigate the relationship between thymic function a...

Research paper thumbnail of The Nerve Growth Factor Receptor (NGFR/p75NTR): A Major Player in Alzheimer’s Disease

International Journal of Molecular Sciences

Alzheimer’s disease (AD) represents the most prevalent type of dementia in elderly people, primar... more Alzheimer’s disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aβ) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space (amyloid plaques) and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; tangles or neurofibrillary aggregates). The Nerve growth factor receptor (NGFR/p75NTR) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., proNGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aβ peptides can blind to NGFR/p75NTR making it the “ideal” candidate in mediating Aβ-induced neuropathology. In addition to pathogenesis and neuropathology, several data indicated that NGFR/p75NTR could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75NTR could represent a good diagnostic tool, as well a...

Research paper thumbnail of Prioritization of Drug Targets for Neurodegenerative Diseases by Integrating Genetic and Proteomic Data From Brain and Blood

Research paper thumbnail of Expression and Signaling Pathways of Nerve Growth Factor (NGF) And Pro-NGF in Breast Cancer: A Systematic Review

Breast cancer represents the most frequent cancer and the leading cause of cancer death among wom... more Breast cancer represents the most frequent cancer and the leading cause of cancer death among women. Thus, the prevention and early diagnosis of breast cancer appears to be of primary urgency as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor that plays a key role in the regulation of neuronal functions thought the binding to the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). Also, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin or by binding to TrkA receptors with low affinity. Both in vitro and in vivo studies showed that NGF is synthesized and released by breast cancer cells and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signal...

Research paper thumbnail of Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Research paper thumbnail of Epidemiology and genetics of frontotemporal dementia: a door-to-door survey in Southern Italy

Neurobiology of Aging, Dec 1, 2012

Objectives-To estimate FTD prevalence, identify FTD-related mutations, correlate FTD phenotype wi... more Objectives-To estimate FTD prevalence, identify FTD-related mutations, correlate FTD phenotype with mutations in a Southern Italian population. Methods-Study population consisting of subjects ≥50 years of age residing in the Community of Biv. on January 1, 2004. Door-to-door two-phase design. Genetic and biochemical analyses were done on samples collected from 32 patients. Results-Prevalence rates were 0.6 for AD, 0.4 for VD, 3.5 for FTD, 0.2 for Parkinson Dementia and 1.2 for unspecified dementia. Three GRN (one known and two novel) mutations with reduced plasma protein levels were found associated to three distinct phenotypes (behavioural, affective and delirious type).

Research paper thumbnail of Genetic variation in APOE, GRN, and TP53 are phenotype modifiers in frontotemporal dementia

Neurobiology of Aging, Mar 1, 2021

Frontotemporal dementia (FTD) is a clinical, genetic, and pathologic heterogeneous group of neuro... more Frontotemporal dementia (FTD) is a clinical, genetic, and pathologic heterogeneous group of neurodegenerative diseases. In this study, we investigated the role of APOƐ4, rs5848 in GRN, and rs1042522 in TP53 gene as disease risk factors and/or phenotype modifiers in 440 FTD patients, including 175 C9orf72 expansion carriers. We found that the C9orf72 expansion carriers showing an earlier age at onset (p < 0.001). Among the clinical groups, the FTD-MND (motoneuron disease) showed the lowest survival (hazard ratio [HR] ¼ 4.12), and the progressive nonfluent aphasia group showed the highest onset age (p ¼ 0.03). In our cohort, the rs1042522 in TP53 was associated with disease onset (p ¼ 0.02) and survival (HR ¼ 1.73) and rs5848 GRN with a significantly shorter survival in CC homozygous patients (HR ¼ 1.98). The frequency of APOƐ4 carriers was significantly increased in the C9orf72 noncarriers (p ¼ 0.022). Although validation of our findings is necessary, our results suggest that TP53, GRN, and APOE genes may act as phenotype modifiers in FTD and should be considered in future clinical trials.

Research paper thumbnail of P3-404: Presenilins mutations are frequent in early-onset familial frontotemporal dementia

Alzheimers & Dementia, Jul 1, 2006

... Raffaele Maletta1 email address , Rosanna Colao1, Sabrina Anna Maria Curcio1, Francesca Frang... more ... Raffaele Maletta1 email address , Rosanna Colao1, Sabrina Anna Maria Curcio1, Francesca Frangipane1, Maria Mirabelli1, Gianfranco Puccio1, Maria Anfossi1, Livia Bernardi1, Angela Costanzo1, Francesca Ferrise1, Maura Gallo1,.

Research paper thumbnail of Neurodegenerative clinical records analyzer: detection of recurrent patterns within clinical records towards the identification of typical signs of neurodegenerative disease history

JLIS.it, May 15, 2023

Neurodegenerative clinical records analyzer: detection of recurrent patterns within clinical reco... more Neurodegenerative clinical records analyzer: detection of recurrent patterns within clinical records towards the identification of typical signs of neurodegenerative disease history* Erika Pasceri (a) , Mérième Bouhandi (b) , Claudia Lanza (c) , Anna Perri (d) , Valentina Laganà (e) , Raffaele Maletta (f) , Raffaele Di Lorenzo (g) , Amalia C. Bruni (h)

Research paper thumbnail of Nicastrin gene in familial and sporadic Alzheimer's disease

Neuroscience Letters, Dec 1, 2003

Nicastrin is a protein recently discovered associated to presenilins and involved in the producti... more Nicastrin is a protein recently discovered associated to presenilins and involved in the production of amyloid beta peptide that accumulates in Alzheimer's disease (AD) brain. In this study the nicastrin gene was examined for unknown mutations and polymorphisms in 104 patients with familial AD (52 early-onset and 52 late-onset), 174 sporadic AD and 191 healthy neurological controls of Italian origin. The scanning of the nicastrin gene identified a missense mutation (N417Y) in two patients with sporadic AD, in an early-onset familial AD and in a young control subject. Furthermore, we found two silent mutations and four intronic polymorphisms, three of them co-segregating in a single haplotype. We found some differences in the distribution of genotype alterations in the AD population compared to the controls. However, our data together with other evidence did not support the pathological role of missense mutation N417Y.

Research paper thumbnail of AβPP A713T Mutation in Late Onset Alzheimer's Disease with Cerebrovascular Lesions

Journal of Alzheimer's Disease, Jun 5, 2009

Mutations in the amyloid-beta protein precursor (AbetaPP) gene can cause autosomal dominant early... more Mutations in the amyloid-beta protein precursor (AbetaPP) gene can cause autosomal dominant early-onset Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease, or Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) associated with cerebral amyloid angiopathy (CAA), cerebral hemorrhage, or both. We have previously reported that the AbetaPP A713T mutation is associated with AD and subcortical ischemic lesions at magnetic resonance imaging in a large family which neuropathology confirmed CAA, stroke, and AD lesions. The objective of this clinical and molecular study was to investigate AbetaPP gene mutations in 59 patients affected by AD with cerebrovascular lesions (CVLs) and a family history of dementia. We identified three affected subjects with the AbetaPP A713T mutation. Since the prevalence of this mutation worldwide is very low, a common founder could exist in southern Italy. The pathogenicity of this mutation was confirmed and the clinical AD phenotype with CVLs seems to be a distinctive feature in the southern Italian population. The identification of these patients suggests that genetic epidemiology in large cohorts of familial late onset AD with CVLs would increase the probability of identifying AbetaPP mutations.

Research paper thumbnail of A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene

Neurology, Sep 13, 2004

Three members of an Italian family with autosomal dominant dementia and multiple strokes had the ... more Three members of an Italian family with autosomal dominant dementia and multiple strokes had the A713T mutation of the APP gene. The neuropathologic examination of the proband disclosed Alzheimer disease (AD) with severe cerebral amyloid angiopathy and multiple infarcts. This indicates that the A713T mutation of the APP gene, lying at the ␥-secretase cleavage site, can be responsible for AD with symptomatic cerebral amyloid angiopathy.

Research paper thumbnail of P3-166: Epidemiology of Frontotemporal dementia in southern Italy

Alzheimers & Dementia, Jul 1, 2009

... Francesca Frangipane; Rosanna Colao; Gianfranco Puccio; Sabrina AM Curcio; Maria Mirabelli; R... more ... Francesca Frangipane; Rosanna Colao; Gianfranco Puccio; Sabrina AM Curcio; Maria Mirabelli; Raffaele Maletta; Maria Anfossi; Livia Bernardi; Maura Gallo; Silvana Geracitano; Carmine Tomaino; Maria G. Muraca; Alessandra Clodomiro; Raffaele Di Lorenzo; Francesco ...

Research paper thumbnail of Circulating Levels of Soluble Receptor for Advanced Glycation End Products in Alzheimer Disease and Vascular Dementia

Archives of neurology, Nov 1, 2005

Background: The receptor for advanced glycation end products (RAGE) is a cell surface receptor th... more Background: The receptor for advanced glycation end products (RAGE) is a cell surface receptor that has been implicated in vascular disease and neurodegeneration. Low levels of its secreted isoform, soluble RAGE (sRAGE), have been regarded as a putative risk factor for atherosclerosis. In addition, administration of sRAGE has been shown to reduce development of cerebral ␤-amyloidosis in an Alzheimer disease mouse model. Objective: To investigate the role of sRAGE as a biological marker for Alzheimer disease and vascular dementia. Design: Cross-sectional study of 152 patients with a clinical diagnosis of Alzheimer disease, 91 with vascular dementia and 161 control subjects. Main Outcome Measure: Plasma levels of sRAGE. Results: Levels of sRAGE were significantly reduced in the plasma of patients with Alzheimer disease compared with that for those with either vascular dementia (PϽ.05) or with controls (PϽ.001). Conclusions: Patients with Alzheimer disease have reduced levels of sRAGE in plasma compared with patients with vascular dementia and controls. The striking reduction of circulating sRAGE in Alzheimer disease further supports a role for the RAGE axis in this clinical entity and requires further investigation.

Research paper thumbnail of Using the Theory of Planned Behavior and Past Behavior to Explain the Intention to Receive a Seasonal Influenza Vaccine among Family Caregivers of People with Dementia

International journal of translational medicine, May 19, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of P1-303: Low levels of sRAGE plasma concentration in different types of dementia

Alzheimers & Dementia, Jul 1, 2006

Background: Late-onset Alzheimer's disease is a complex neurodegenerative disorder characterized ... more Background: Late-onset Alzheimer's disease is a complex neurodegenerative disorder characterized by cognitive decline and distinct neuropathology. Multiple genes will be linked/associated with the disease. While case/control association studies are informative in the identification of risk factors, large extended pedigrees may be more useful in identifying genetic variants linked with the disease. Objective: To identify the mutations in the candidate genes linked with the disease in our large extended pedigrees. Methods: Our family 28 has 14 siblings, 5 affected with late-onset Alzheimer's disease and two of the father's siblings also affected with the disease. We have DNA on all of the siblings, including the five affected siblings, on the two affected of the father's siblings, on one of the mother's unaffected siblings, on many children and spouses, for a total of 63 samples. The clinical diagnosis was made according to the NINCDS-ADRDA criteria. In addition, we included an MRI of the brain, showing cortical atrophy with no evidence of strokes or tumors. Using a microsatellite scan of the DNA, we identified a location on chromosome 12 with a significant LOD score that was linked with the disease in family 28. Since the location was large containing many genes, we used the 100 K SNP microarrays for further analysis. We have identified several locations on chromosome 12 as well as locations on two other chromosomes that are associated with the disease. We are in the process of analyzing additional tag SNPs and microsatellites in candidate genes, before we begin resequencing to identify the genetic variations linked with the disease in this family. Conclusions: The use of extended pedigrees with multiple affected members may be more useful in identifying genetic variants linked with complex diseases.

Research paper thumbnail of A Clinical, Pathological And Molecular Study Of A Frontotemporal Dementia Sporadic Case

Research paper thumbnail of P1-319: Presenilin 2 Ser130Leu mutation in a case of late-onset “sporadic” AD

Alzheimers & Dementia, Jul 1, 2006

way ANOVA. Results: 78% of the AD cases were ApoE 4/3 (50%) or 4/4 (28%), while 32% were 3/3. Apo... more way ANOVA. Results: 78% of the AD cases were ApoE 4/3 (50%) or 4/4 (28%), while 32% were 3/3. ApoE 4/4 carriers had a younger age at onset (66Ϯ5 years, mean Ϯ SD) than 3/4 (69Ϯ7) and 3/3 carriers (71Ϯ6) but without statistical difference. The distribution of Apo E concordant sibpairs (nϭ22) was the following: 3/3 (nϭ4 sib-pairs, differences in age at onset 7.2Ϯ6.4 years), 3/4 (nϭ11, 4.5Ϯ3.0 years), 4/4 (nϭ7, 6.5Ϯ3.4 years). ApoE discordant sib-pairs (nϭ12) were the following: 3/4 versus 4/4 (nϭ8 sib-pairs, differences in age at onset 4.2Ϯ2.4 years), and 3/3 versus 3/4 (nϭ4, 5.5Ϯ1.9 years). Differences in age at onset in concordant ApoE sib-pairs (5.7Ϯ3.9 years) were not significantly different than in discordant sib-pairs (4.6Ϯ2.3 years). The presence of an extra ApoE allele in discordant sib-pairs only meant a younger age at onset in half of the pairs. Conclusions: Within sib-pairs with familial AD, ApoE genotype is not a major factor influencing age at onset. Other variables should be considered to influence the great variability in age at onset among affected siblings.

Research paper thumbnail of The Nerve Growth Factor Receptor (NGFR/P75<sup>ntr</sup>): A Major Player in Alzheimer’s Disease

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of The Shortening of Leukocyte Telomere Length Contributes to Alzheimer’s Disease: Further Evidence from Late-Onset Familial and Sporadic Cases

Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stabili... more Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are considered markers of premature cellular senescence. This is believed to contribute to age-related diseases, including Alzheimer's disease (AD) and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case-control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, which were all from Calabria, a region from south Italy. Following regression analysis, telomeres were found to be significantl...

Research paper thumbnail of Thymic function and survival at advance ages in nursing home residents from Southern Italy

Immunity & Ageing

Background Immunosenescence is a complex process characterized by an age-related remodelling of i... more Background Immunosenescence is a complex process characterized by an age-related remodelling of immune system. The prominent effects of the immunosenescence process is the thymic involution and, consequently, the decreased numbers and functions of T cells. Since thymic involution results in a collapse of the T-cell receptor (TCR) repertoire, a reliable biomarker of its activity is represented by the quantification of signal joint T-cell receptor rearrangement excision circles (sjTRECs) levels. Although it is reasonable to think that thymic function could play a crucial role on elderly survival, only a few studies investigated the relationship between an accurate measurement of human thymic function and survival at old ages. Methods and findings By quantifying the amount sjTRECs by real-time polymerase chain reaction (PCR), the decrease in thymic output in 241 nursing home residents from Calabria (Southern Italy) was evaluated to investigate the relationship between thymic function a...

Research paper thumbnail of The Nerve Growth Factor Receptor (NGFR/p75NTR): A Major Player in Alzheimer’s Disease

International Journal of Molecular Sciences

Alzheimer’s disease (AD) represents the most prevalent type of dementia in elderly people, primar... more Alzheimer’s disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aβ) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space (amyloid plaques) and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; tangles or neurofibrillary aggregates). The Nerve growth factor receptor (NGFR/p75NTR) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., proNGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aβ peptides can blind to NGFR/p75NTR making it the “ideal” candidate in mediating Aβ-induced neuropathology. In addition to pathogenesis and neuropathology, several data indicated that NGFR/p75NTR could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75NTR could represent a good diagnostic tool, as well a...

Research paper thumbnail of Prioritization of Drug Targets for Neurodegenerative Diseases by Integrating Genetic and Proteomic Data From Brain and Blood

Research paper thumbnail of Expression and Signaling Pathways of Nerve Growth Factor (NGF) And Pro-NGF in Breast Cancer: A Systematic Review

Breast cancer represents the most frequent cancer and the leading cause of cancer death among wom... more Breast cancer represents the most frequent cancer and the leading cause of cancer death among women. Thus, the prevention and early diagnosis of breast cancer appears to be of primary urgency as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor that plays a key role in the regulation of neuronal functions thought the binding to the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). Also, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin or by binding to TrkA receptors with low affinity. Both in vitro and in vivo studies showed that NGF is synthesized and released by breast cancer cells and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signal...