Sortilin C-terminal fragment deposition depicts tangle-related nonamyloid neuritic plaque growth in Alzheimer's disease DOI Open Access

Qi-Lei Zhang,

Yan Wang, S. Coulibaly

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 14, 2024

Abstract Sortilin C-terminal fragments (sorfra) can co-deposit in β-amyloid (Aβ) plaques human brain. However, sorfra develop the cerebrum with a spatiotemporal trajectory as of tauopathy. Here we examined pathogenesis relative to neuritic plaque evolution brains amyloid and tau pathologies converged neocortex hippocampus. Sorfra occurred correlation pTau/tangle, but not Aβ, across cerebral regions, neighboring cortical/hippocampal areas, along sulcal valley gyral hilltop transition. were matchable location, shape size between consecutive sections, colocalized double-labeling preparations. Microscopical study tissue clearance three-dimensional imaging revealed sorfra/Aβ well independent plaques. Among former, labeling correlated negatively Aβ/amyloid β-secretase-1 dystrophic neurites. depleted microtubule-associated protein 2 (MAP2) labeled neuronal somata dendrites, whereas normal looking MAP2/sortilin co-labeled profiles nearby. deposits seen astrocytes microglia around Taken together, are anatomically silver stained They tangle-related somatodendritic degeneration, presenting nonamyloid growth Aβ formation Aβ-independent during Alzheimer’s disease pathogenesis.

Language: Английский

Evolution of Human Susceptibility to Alzheimer's Disease: A Review of Hypotheses and Comparative Evidence DOI Open Access

Isabel August,

Pascal Gagneux, Katerina Semendeferi

et al.

Evolutionary Anthropology Issues News and Reviews, Journal Year: 2025, Volume and Issue: 34(1)

Published: Jan. 13, 2025

Primates rely on memory to navigate both physical and social environments in humans, loss of function leads devastating consequences. Alzheimer's disease (AD) is a neurodegenerative which begins by impacting functioning ultimately fatal. AD common across human populations its prevalence predicted rise with increases the aging population. Despite this, full phenotype has not been observed any other nonhuman primate species. While significant amount research devoted understanding immediate mechanisms involved pathogenesis less focused why humans are particularly vulnerable diseases like AD. Here we explore hypotheses evolution distinct susceptibility place these context findings from comparative neuroanatomical molecular studies discuss recent evidence for evolutionary changes protective against lineage.

Language: Английский

Citations

0
Research progress of cell senescence in Alzheimer's disease: mechanisms and therapy DOI
Jingwen Cai, Lin Yang,

Yuewei Xu

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177697 - 177697

Published: May 1, 2025

Language: Английский

Citations

0
Sortilin C-terminal fragment deposition depicts tangle-related nonamyloid neuritic plaque growth in Alzheimer's disease DOI Open Access

Qi-Lei Zhang,

Yan Wang, S. Coulibaly

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 14, 2024

Abstract Sortilin C-terminal fragments (sorfra) can co-deposit in β-amyloid (Aβ) plaques human brain. However, sorfra develop the cerebrum with a spatiotemporal trajectory as of tauopathy. Here we examined pathogenesis relative to neuritic plaque evolution brains amyloid and tau pathologies converged neocortex hippocampus. Sorfra occurred correlation pTau/tangle, but not Aβ, across cerebral regions, neighboring cortical/hippocampal areas, along sulcal valley gyral hilltop transition. were matchable location, shape size between consecutive sections, colocalized double-labeling preparations. Microscopical study tissue clearance three-dimensional imaging revealed sorfra/Aβ well independent plaques. Among former, labeling correlated negatively Aβ/amyloid β-secretase-1 dystrophic neurites. depleted microtubule-associated protein 2 (MAP2) labeled neuronal somata dendrites, whereas normal looking MAP2/sortilin co-labeled profiles nearby. deposits seen astrocytes microglia around Taken together, are anatomically silver stained They tangle-related somatodendritic degeneration, presenting nonamyloid growth Aβ formation Aβ-independent during Alzheimer’s disease pathogenesis.

Language: Английский

Citations

0