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Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Iowa, Iowa City, IA, USA.
Background: It is increasingly apparent that tau pathology in Alzheimer's disease (AD) begins in the brainstems of middle-aged patients, decades before the onset of symptoms. Most studies are, however, based on brain-bank cohorts and focus on patients dying of natural causes. The true incidence of tau pathology in the brainstem thus remains unclear.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Iowa, Iowa City, IA, USA.
Background: Sorbs2 is a cytoskeletal adaptor protein that is expressed in hippocampal neurons, but its mechanistic role in these cells is not yet fully understood.
Method: We created two groups of mice for our study: whole-body Sorbs2-Knockout (KO) mice and Sorbs2-Flox mice, which had neuronal knockout via AAV-PHP.eB-hSyn1-Cre virus injection.
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of California, Berkeley, Berkeley, CA, USA.
Background: The amyloid cascade hypothesis posits a sequence of events proceeding from amyloid-β (Aβ) deposition to entorhinal cortical (EC) tau to neocortical (meta-temporal) tau. This study examined how genetics may modify relationships between these variables on the AD pathway.
Methods: We used causal path analyses to model effects of sex, APOE-ε4 (0,1,2 alleles), and genetic risk for neuroinflammation on Aβ, EC tau and meta temporal tau.
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Iowa, Iowa City, IA, USA.
Background: The dorsal raphe nucleus (DRN) is the primary source of serotonergic projections to supratentorial structures. We and others have shown that it is selectively vulnerable to tau pathology in both human and mouse models of early AD. Although well characterized in mice, the neurochemical anatomy of the human DRN, and in particular the role of Vesicular glutamate transporter-3 (VGLUT3)-expressing neocortical projection neurons in tau pathology, remains unclear.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Stanford University, School of Medicine, Stanford, CA, USA.
Background: Alzheimer's disease (AD) is the most common form of dementia. Neuropathologically, AD stands out as a mixed proteinopathy. Beta-amyloid and tau biomarkers can now add in-vivo support to the AD diagnosis.
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