Cerebrospinal fluid β-amyloid1–42 and tau in control subjects at risk for Alzheimer’s disease: The effect of APOE ε4 allele (original) (raw)
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Journal of Alzheimer's disease : JAD, 2010
In Alzheimer's disease (AD), the cerebral pathological changes begin many years before the clinical manifestation of the disease. Biomarkers for AD, such as the cerebrospinal fluid (CSF) concentrations of amyloid-β1-42 (Aβ1-42) and tau phosphorylated at threonine 181 (pTau181), may reflect these cerebral changes relatively early. Accordingly, cognitively healthy subjects at risk for AD often have altered CSF concentrations of Aβ1-42 and pTau181. In this study, we assessed the effects and interaction of two strong risk factors for AD, aging and the presence of the APOEε4 allele, on the CSF Aβ1-42 and pTau181 concentrations in 280 adults with normal cognition across the lifespan. For comparison, we further included 152 patients with probable AD. We found significant effects of age on the CSF Aβ1-42 and pTau181, and of the APOEε4 genotype on the Aβ1-42 levels in the cognitively normal participants. Carrying the APOEε4 allele was associated with a significant decrease of the Aβ1-42 ...
1998
SUMMARY To better de®ne the in¯uence of apolipoprotein E (ApoE) e4 genotype on the cognitive and biochemical features of Alzheimer's disease (AD), cross-sectional analysis of global cognitive measures and cerebrospinal ¯uid studies gathered on AD subjects at a tertiary care facility between 1986 and 1997 was carried out. The 112 AD patients examined included 62 women and 50 men with a mean (SD) age of 64.2 (9.2) years. Patient demographics, illness onset age and duration, education level and global cognitive measures were recorded systematically. Genetic analysis for ApoE allele type and biochemical characterization of CSF, including total tau concentration, was performed. Descriptive statistics of demographics, cognitive and CSF measures were performed by chi-square, ANOVA and Tukey's tests. Overrepresentation of the e4 allele was found, with 45.5% of AD patients heterozygous and 20.5% homozygous for ApoE e4. Overall, ApoE e4 status had no eect on mean onset age of AD (F 1.56; p 0.214), but an earlier mean onset age of AD (F 4.10; p 0.02) was seen in the late-onset subjects. No dierences were found with regard to ApoE e4 status and measures of disease, duration of illness or global cognitive performance. Although CSF tau was elevated in our sample (575.4+290.3 pg/ml), ApoE e4 status did not in¯uence total CSF tau or neurotransmitter metabolite levels. ApoE e4 genotype had no impact on a variety of illness severity, cognitive and CSF examinations in the largest cross-sectional analysis of AD subjects yet reported. # 1998 US Government.
Stability of CSF β-Amyloid1–42 and Tau Levels by APOE Genotype in Alzheimer Patients
Dementia and Geriatric Cognitive Disorders, 2006
Background: Cerebrospinal fluid (CSF) measures of β-amyloid1–42 and tau differ between patients with Alzheimer’s Disease (AD) and elderly normal controls. The effect of time and APOE genotype on these biomarkers continues to be elucidated. Methods: We assessed CSF β-amyloid1–42 and tau in 20 mild-to-moderate AD patients, 11 APOE Ε4+ and 9 APOE Ε4–, over a mean time of 3.8 years (range 1–11.1 years). Results: Over the period measured, CSF β-amyloid1–42 levels were lower in APOE Ε4+ compared to APOE Ε4– patients, and the levels decreased over time. Tau levels were stable over time and did not show an effect of APOE allele. Conclusions: While this is a limited clinical sample, the further decrease in CSF β-amyloid1–42 (i.e., more abnormal) combined with the CSF tau stability over a mean period of almost 4 years suggests that β-amyloid1–42 and tau maintain their potential usefulness as diagnostic biomarkers over time. These findings should be taken into account if CSF β-amyloid1–42 and ...
Journal of Neurology, 2014
Polymorphism of the apolipoprotein E gene (APOE) plays a role in the level of neuropathological lesions and in drug response in Alzheimer's disease (AD). The aim of this study was to investigate whether the selection of AD patients based on cerebrospinal fluid (CSF) biomarkers assessment may be biased by their APOE distribution. We studied the relationships between APOE genotype and CSF biomarkers levels in a total of 432 patients (AD, n = 244; non-AD, n = 188) explored for cognitive disorders. We studied the distribution of APOE genotypes among AD patient subgroups selected by various cut-offs of CSF biomarkers. Strategies of screening based on CSF Ab1-42 lead to overselection of e4/e4 patients in the AD group. Screening based on tau levels did not change Apoe4 distribution in the AD group. CSF Ab1-42 discriminated better AD patients with at least one e4 than AD patients with no e4. A strong allele-effect relationship was detected between APOE genotype and CSF amyloid-b (Ab1-42) in AD patients. Selecting AD patients on CSF amyloid levels only may create an overselection of e4/e4 carriers, and might potentially bias the population of patients included in clinical trial studies.
ApoE Alleles and Tau Markers in Patients with Different Levels of Cognitive Impairment
Archives of Medical Research, 2005
Background. The presence of brain hyperphosphorylated tau constitutes a hallmark of neurodegenerative disorders of the Alzheimer's type. This report describes the relationships between tau markers in the cerebrospinal fluid (CSF), the degree of cognitive impairment and the predictive value of genetic markers such the alleles of apolipoprotein E, namely, the presence of Apo-ε4, as part of a longitudinal study. Methods. Three major groups of patients with ages ranging from 65-73 years were evaluated in this study (n ϭ 72): Alzheimer's disease patients (AD), a group with mild cognitive impairment (MCI) and normal senile patients (NS). Hyperphosphorylated tau and tau dephosphorylated species at the Alzheimer-type epitopes in CSF samples were analyzed by ELISA assays using a battery of different monoclonal antibodies. ApoE was analyzed by PCR in blood samples.
Alzheimer's & Dementia, 2012
In Alzheimer's disease (AD), the cerebral pathological changes begin many years before the clinical manifestation of the disease. Biomarkers for AD, such as the cerebrospinal fluid (CSF) concentrations of amyloid-,81-42 (A,Bl-42) and tau phosphorylated at threonine 181 (pTau181), may reflect these cerebral changes relatively early. Accordingly, cognitively healthy subjects at risk for AD often have altered CSF concentrations of A,Bl-42 and pTau181. In this study, we assessed the effects and interaction of two strong risk factors for AD, aging and the presence of the APOEc4 allele, on the CSF A,Bl-42 and pTau181 concentrations in 280 adults with normal cognition across the lifespan. For comparison, we further included 152 patients with probable AD. We found significant effects of age on the CSF A,Bl-42 and pTau181, and of the APOEc4 genotype on the A,Bl-42 levels in the cognitively normal participants. Carrying the APOEc4 allele was associated with a significant decrease of the A,Bl-42 concentrations in middle-aged and older participants. In the group of participants with AD, the A,Bl-42 levels were significantly lower in the APOEc4 carriers compared to the non-carriers. These findings demonstrate significant age effects on the CSF A,B 1 _ 42 and pTau181 across lifespan. They also suggest that the decrease of A,Bl-42, but not the increase ofpTaul81 CSF levels is accelerated by the APOEc4 genotype in middle-aged and older adults with normal cognition. of cerebrospinal fluid (CSF) A.B 1 -4 2 and pTau concentrations can already be detected in asymptomatic older subjects at risk for AD [1 ,2], and predict cognitive decline in cognitively healthy older adults and in subjects with mild cognitive impairment . The presence of the apolipoprotein c4 (APOEc4) allele is a well-established genetic risk factor for AD. Carrying the APOEc4 allele may accelerate the pathophysiological process [7) and lower the age of clinical onset of the disease . Some postmortem studies [I 0,11 ], but not all , have found associations of the APOEc4 genotype with higher levels of amyloid plaque deposition and neurofibrillary pathology. Studies on the associations of CSF biomarker levels with
Apo-E4 Allele in Conjunction with Aβ42 and Tau in CSF: Biomarker for Alzheimers Disease
Current Alzheimer Research, 1970
The objective of this study was to elucidate an association between Apo-E 4 allele and CSF biomarkers A 42 and tau for the diagnosis of Alzheimer's Disease (AD) patients. A 42 and tau protein concentrations in CSF were measured by using ELISA assays. The levels of A 42 were found to be decreased where as tau levels increased in AD patients. Moreover in AD patients Apo-E 4 allele carriers have shown low A 42 levels (328.86 ± 99.0 pg/ml) compared to Apo-E 4 allele non-carriers (367.52 ± 5 7.37 pg/ml), while tau levels were higher in Apo-E 4 allele carriers (511 ± 44.67 pg/ml) compared to Apo-E 4 allele non-carriers (503.75 ± 41.08 pg/ml). Combination of A 42 and tau resulted in sensitivity of 75.38% and specificity of 94.82% and diagnostic accuracy of 84.30% for AD compared with the controls. Therefore low A 42 and elevated tau concentrations in CSF may prove to be a better diagnostic marker for AD along with the Apo-E 4 allele.
Journal of Neural Transmission
ApoE4, the strongest genetic risk factor for Alzheimer’s disease (AD), has been shown to be associated with both beta-amyloid (Aβ) and tau pathology, with the strongest evidence for effects on Aβ, while the association between ApoE4 and tau pathology remains inconsistent. This study aimed to investigate the associations between ApoE4 with CSF Aβ42, total tau (t-tau), phospho-tau181 (p-tau), and with the progression of decline in a large cohort of MCI subjects, both progressors to AD and other dementias, as well as non-progressors. We analyzed associations of CSF Aβ42, p-tau and t-tau with ApoE4 allele frequency cross-sectionally and longitudinally over 3 years of follow-up in 195 individuals with a diagnosis of MCI-stable, MCI-AD converters and MCI progressing to other dementias from the German Dementia Competence Network. In the total sample, ApoE4 carriers had lower concentrations of CSF Aβ42, and increased concentrations of t-tau and p-tau compared to non-carriers in a gene dose...