@article{1f7e2f0d48774f78bbe84d23fc1be5ce,
title = "C99 selectively accumulates in vulnerable neurons in Alzheimer's disease",
abstract = "Introduction: 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.",
keywords = "Alzheimer's disease, Amyloid hypothesis, C99, Proximity-ligation assay, bCTF, β-amyloid",
author = "Pulina, {Maria V.} and Maya Hopkins and Vahram Haroutunian and Paul Greengard and Victor Bustos",
note = "Funding Information: The authors thank Dr. Fred Gorelick and Dr. Yotam Sagi for discussion and Dr. Jean-Pierre Roussarie for providing reagents and for discussion. They also thank Alison North and the Bio-imaging facility at The Rockefeller University for training and advice in super-resolution microscopy. The authors thank Elisabeth Griggs for figure composition. This work was supported by the Fisher Center for Alzheimer's Research Foundation , The Cure Alzheimer's Fund and JPB Grant 794 (to P.G.). V.B. was supported by DOD / USAMRAA Grant W81XWH-14-1-0045 . This paper is dedicated to the memory of Dr. Paul Greengard. Funding Information: The authors thank Dr. Fred Gorelick and Dr. Yotam Sagi for discussion and Dr. Jean-Pierre Roussarie for providing reagents and for discussion. They also thank Alison North and the Bio-imaging facility at The Rockefeller University for training and advice in super-resolution microscopy. The authors thank Elisabeth Griggs for figure composition. This work was supported by the Fisher Center for Alzheimer's Research Foundation, The Cure Alzheimer's Fund and JPB Grant 794 (to P.G.). V.B. was supported by DOD/ USAMRAA Grant W81XWH-14-1-0045. This paper is dedicated to the memory of Dr. Paul Greengard. Publisher Copyright: {\textcopyright} 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.",
year = "2020",
month = feb,
day = "1",
doi = "10.1016/j.jalz.2019.09.002",
language = "English",
volume = "16",
pages = "273--282",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "John Wiley & Sons Inc.",
number = "2",
}