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C99 selectively accumulates in vulnerable neurons in Alzheimer's disease
Author(s) -
Pulina Maria V.,
Hopkins Maya,
Haroutunian Vahram,
Greengard Paul,
Bustos Victor
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.09.002
Subject(s) - disease , amyloid (mycology) , neuroscience , β amyloid , alzheimer's disease , cognitive impairment , amyloid β , amyloid precursor protein , medicine , pathology , psychology
The levels and distribution of amyloid deposits in the brain does not correlate well with Alzheimer's disease (AD) progression. Therefore, it is likely that amyloid precursor protein and its proteolytic fragments other than amyloid b (Ab) contribute to the onset of AD. Methods We developed a sensitive assay adapted to the detection of C99, the direct precursor of b‐amyloid. Three postmortem groups were studied: control with normal and stable cognition; patients with moderate AD, and individuals with severe AD. The amount of C99 and Aβ was quantified and correlated with the severity of AD. Results C99 accumulates in vulnerable neurons, and its levels correlate with the degree of cognitive impairment in patients suffering from AD. In contrast, Aβ levels are increased in both vulnerable and resistant brain areas. Discussion These results raise the possibility that C99, rather than Aβ plaques, is responsible for the death of nerve cells in AD.