Males vs females: differences in the AB accumulation (original) (raw)
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AβPP/PS1 Transgenic Mice Show Sex Differences in the Cerebellum Associated with Aging
Journal of Alzheimer's Disease, 2016
Cerebellar pathology has been related to presenilin 1 mutations in certain pedigrees of familial Alzheimer's disease. However, cerebellum tissue has not been intensively analyzed in transgenic models of mutant presenilins. Furthermore, the effect of the sex of the mice was not systematically analyzed, despite the fact that important gender differences in the evolution of the disease in the human population have been described. We analyzed whether the progression of amyloidosis in a double transgenic mouse, APP/PS1, is susceptible to aging and differentially affects males and females. The accumulation of amyloid in the cerebellum differentially affects males and females of the APP/PS1 transgenic line, which was found to be tenfold higher in 15-month-old females. Amyloid- accumulation was more evident in the molecular layer of the cerebellum, but glia reaction was only observed in the granular layer of the older mice. The sex divergence was also observed in other neuronal, survival, and autophagic markers. The cerebellum plays an important role in the evolution of the pathology in this transgenic mouse model. Sex differences could be crucial for a complete understanding of this disease. We propose that the human population could be studied in this way. Sex-specific treatment strategies in human populations could show a differential response to the therapeutic approach.
Morphological and quantitative analysis of cerebellar cortical cells in Alzheimer’s disease
Folia Neuropathologica, 2012
Alzheimer's disease (AD) is a neurodegenerative amyloid disease, although a great deal of research has been done, its aetiology is still unknown. In Khachaturian's hypothesis on the involvement of calcium in the aetiology of Alzheimer's disease, particular attention is paid to the disorder of calcium metabolism. Ludo van Bogaert, describing AD, has drawn attention to the presence of a multi-system damage to the brain and described four forms of the disease, including two cerebellar types: cerebellar-pyramidal and cerebellar. The aim of our study was to analyze the expression of calcium-binding proteins (calbindin, calretinin, parvalbumin) in cortical neurons of the cerebellum in patients diagnosed with Alzheimer's disease (experimental group) and in a control group (patients without Alzheimer's disease). We performed the quantitative analysis of the density of Purkinje cells and Bergmann glial cells in the cerebellar cortex. We observed weak immunoreaction with a calretinin antibody in Lugaro cells, and with parvalbumin in Purkinje cells in the experimental group. A weaker expression of calcium-binding proteins in the experimental group may indicate the disturbance of the transport and buffering of intracellular Ca 2+ levels. The quantitative analysis showed that the density of Bergmann glial cells was higher in the experimental group. Our study suggests the disturbance of calcium metabolism in Alzheimer's disease.
Regional and Gender Study of Neuronal Density in Brain during Aging and in Alzheimer's Disease
Frontiers in Aging Neuroscience, 2016
Background: Learning processes or language development are only some of the cognitive functions that differ qualitatively between men and women. Gender differences in the brain structure seem to be behind these variations. Indeed, this sexual dimorphism at neuroanatomical level is accompanied unequivocally by differences in the way that aging and neurodegenerative diseases affect men and women brains. Objective: The aim of this study is the analysis of neuronal density in four areas of the hippocampus, and entorhinal and frontal cortices to analyze the possible gender influence during normal aging and in Alzheimer's disease (AD). Methods: Human brain tissues of different age and from both sexes, without neurological pathology and with different Braak's stages of AD, were studied. Neuronal density was quantified using the optical dissector. Results: Our results showed the absence of a significant neuronal loss during aging in non-pathological brains in both sexes. However, we have demonstrated specific punctual significant variations in neuronal density related with the age and gender in some regions of these brains. In fact, we observed a higher neuronal density in CA3 and CA4 hippocampal areas of non-pathological brains of young men compared to women. During AD, we observed a negative correlation between Braak's stages and neuronal density in hippocampus, specifically in CA1 for women and CA3 for men, and in frontal cortex for both, men and women. Conclusion: Our data demonstrated a sexual dimorphism in the neuronal vulnerability to degeneration suggesting the need to consider the gender of the individuals in future studies, regarding neuronal loss in aging and AD, in order to avoid problems in interpreting data.
Alzheimer's & dementia : the journal of the Alzheimer's Association, 2012
Background: According to a widely accepted hypothesis, the amyloid precursor protein (APP) is processed by two competing pathways: the amyloidogenic b-secretase-mediated pathway or the nonamyloidogenic a-secretase-mediated pathway. APP is cleaved preferentially through the nonamyloidogenic pathway in normal brain, whereas the balance shifts to the amyloidogenic pathway in Alzheimer's disease (AD). The levels of the a-secretase-cleaved soluble APP (sAPPa) and b-secretase-cleaved soluble APP (sAPPb) in cerebrospinal fluid (CSF) are likely to reflect these competing mechanisms. Methods: We investigated the levels and the relationship between sAPPa and sAPPb in the CSF of 64 patients with mild AD, 76 patients with mild cognitive impairment, and 12 cognitively healthy control subjects, as well as the effect of apolipoprotein E genotype and sex on soluble APP levels.
Mechanisms of Ageing and Development, 1999
Age-related changes of glial fibrillary acidic protein (GFAP) immunoreactivity were investigated in the cerebellar cortex of young (3 months), adult (12 months) and old (24 months) rats using immunohistochemical techniques associated with image analysis. In young rats, cell bodies of GFAP-immunoreactive astrocytes were found in the white matter and in the granular layer of cerebellar cortex. Radially-oriented branches of astrocytes which are sited in the granular layer were also observed in the molecular layer. The number of GFAP-immunoreactivity astrocytes of white matter was decreased in adult and old rats in comparison with young cohorts, whereas their size increased progressively from 3 to 24 months old. The number and the size of GFAP-immunoreactive astrocytes of the granular layer was similar in young and adult rats. An increased number and size of GFAP-immunoreactive astrocytes was noticeable in old rats in comparison with younger cohorts. The number of radially oriented branches of the molecular layer was the same in the three age groups investigated. The above results indicate that GFAP-immunoreactive astrocytes of rat : S 0 0 4 7 -6 3 7 4 ( 9 9 ) 0 0 0 0 8 -1 M. Sabbatini et al. / Mechanisms of Ageing and De6elopment 108 (1999) 165-172 166 cerebellar cortex undergo age-related changes. The not homogeneous sensitivity to aging of cerebellar astrocytes suggests that evaluation of changes of different cell populations of cerebellar cortex should represent an important step of research on aging cerebellum.