期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 65, 期 2, 页码 659-682出版社
IOS PRESS
DOI: 10.3233/JAD-180179
关键词
Alzheimer's disease; non-demented with AD-like pathology; postsynaptic density proteome; synapse
资金
- Alzheimer's Art Quilt Initiative
- National Institute of Environmental Health Sciences of the National Institutes of Health [T32ES007254]
- National Institute On Aging of the National Institutes of Health [R01AG042890, F31AG057217]
Some individuals, here referred to as Non-Demented with Alzheimer's Neuropathology (NDAN), retain their cognitive function despite the presence of amyloid plaques and tau tangles typical of symptomatic Alzheimer's disease (AD). In NDAN, unlike AD, toxic amyloid-beta oligomers do not localize to the postsynaptic densities (PSDs). Synaptic resistance to amyloid-beta in NDAN may thus enable these individuals to remain cognitively intact despite the AD-like pathology. The mechanism(s) responsible for this resistance remains unresolved and understanding such protective biological processes could reveal novel targets for the development of effective treatments for AD. The present study uses a proteomic approach to compare the hippocampal postsynaptic densities of NDAN, AD, and healthy age-matched persons to identify protein signatures characteristic for these groups. Subcellular fractionation followed by 2D gel electrophoresis and mass spectrometry were used to analyze the PSDs. We describe fifteen proteins which comprise the unique proteomic signature of NDAN PSDs, thus setting them apart from control subjects and AD patients.
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