P2‐237: Neuropathological and biochemical characterization of the oldestold with and without Alzheimer's disease
Year: 2011
Type: article
Study design: Observational Study
Abstract: Alzheimer's disease (AD) biochemistry has been studied extensively, but the precise role(s) of amyloid-beta (Aß) in the instigation of dementia remains obscure. It is essential to establish a complete roster of dementia-associated molecules. Utilizing non-demented high pathology control (ND-HPC) cases harboring autopsy-confirmed Aß deposits, we examined twenty-three protein markers present in the brains of cognitively intact and demented individuals in order to assess the molecular profiles associated with normal cognition. We examined Aß profiles, amyloid precursor protein (APP), tau and other disease-related markers in individuals (87 years and older) exhibiting AD neuropathology with and without clinical dementia. Eighteen ND-HPC and 6 AD subjects were investigated by ELISAs and a battery of Western blots to determine the expression of Aß, APP, tau, a-synuclein, and a variety of other markers related to aging, inflammation and neurodegeneration. Mean Braak stage values for AD and ND-HPC groups were 5.3 and 3.9, respectively although neuropathological analyses of total plaque score, cerebral amyloid angiopathy score, white matter rarefaction score and NFT score exhibited no significant differences. No obvious differences in ApoE allelic frequency were apparent between the groups. ELISA revealed that mean Aß40 levels extracted using glass-distilled formic acid/guanidine hydrochloride were significantly different, although the AD group contained 2 outliers. A11 (oligomer), IDE, PEDF, BDNF were significantly elevated in AD patients while APP, BACE, VEGF, and ApoE levels in AD were significantly decreased compared to ND-HPC. AD is often defined in relation to amyloid deposits, although our experiments reveal that neither plaque density nor Aß peptide levels are strongly associated with dementia. In addition, NFT pathology was less abundant in the ND-HPC group. Other angiogenesis-associated markers such as PEDF and VEGF exhibit inverse quantitative relationships in AD patients. Decreased quantities of APP and ApoE in AD suggest impaired synthesis or enhanced turnover. Interestingly, BACE and IDE levels are decreased and elevated in AD respectively, suggesting an altered equilibrium between the synthesis and degradation of Aß. The elevated amounts of truncated proBDNF (28 kDa) in AD suggest aberrant proteolytic processing with potential consequential effects on brain homeostasis.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1971783075