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SYNAPTIC ACCUMULATION OF APP-C99 IN DIFFERENT FORMS OF ALZHEIMER'S DISEASE
Abstract
Aims
Different groups recently shown APP-C99 accumulation in the brain of animal models of Alzheimer’s disease (AD) and of patients with sporadic (SAD) and autosomal-dominant AD (ADAD). The aim of this study was to determine whether APP-C99 accumulates in synapses in AD.
Methods
We isolated synaptosomal fractions from frozen frontal cortex (n=38) and temporal cortex (n=38) tissue blocks provided by the Neurological Tissue Brain Bank-IDIBAPS. We used postmortem brain samples of patients with SAD (n=10), ADAD (n=10), Down syndrome with AD (n=10) and healthy controls without AD changes (n=8). We performed Western Blot to confirm the presence of APP-C99 in synaptosomes. We measured APP-C99 and Aβ40 concentrations in brain homogenates and in synaptosomes across groups using commercially available immunoassays (APP-β-CTF:IBL America; APP-Amyloid-β (1-40) Aβ:IBL America)
Results
Our results showed that APP-C99 is increased in synapsis in frontal and temporal cortex. APP-C99 is increased in genetic forms of AD in frontal cortex and in all pathological conditions in temporal cortex. Concentrations of APP-C99 in homogenates and synaptosomes correlated with each other. Aβ40 levels in synaptosomes showed no differences between brain regions. Aβ40 concentrations in synaptosomes were significantly increased in SAD, ADAD and DS in temporal and frontal cortex. Interestingly, there is a positive correlation of APP-C99 and Aβ40 levels in synaptosomes in frontal and temporal cortex.
Conclusions
Our data reveal that APP-C99 accumulates in synapses in sporadic and genetic forms of AD suggesting a potential role of APP-C99 in the synaptic damage in AD. Therapies aimed at mitigating APP-C99 accumulation could be potentially beneficial in AD.