Alzheimer’s disease and its co-pathologies: implications for hippocampal degeneration, cognitive decline, and the role ofAPOEε4 DOI Creative Commons
Klara Gawor, Sam Verrept, Geethika Arekatla

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Abstract INTRODUCTION In neurodegenerative dementias, the co-occurrence and interaction of Aβ, tau, other pathological lesions confound their individual contributions to neurodegeneration modulation by risk factors. METHODS We analyzed 480 post-mortem human brains (ages 50–99) using regression structural equation models assess relationships among LATE-NC, α-synuclein, age-related lesions, APOE ε4, as well effects on CA1 neuronal density, brain weight, cognitive status. RESULTS amygdala-predominant α-synuclein pathology were highly interconnected. Tau was strongest predictor global neurodegeneration, while LATE-NC primarily, but not exclusively, affected hippocampal neuron loss. Small vessel disease correlated with both ε4 mainly associated extracellular capillary Aβ. DISCUSSION Although Alzheimer’s plays a central role in degeneration, coexisting pathologies can exacerbate independently contribute it. These factors should be considered patient stratification.

Language: Английский

Alzheimer’s disease and its co-pathologies: implications for hippocampal degeneration, cognitive decline, and the role ofAPOEε4 DOI Creative Commons
Klara Gawor, Sam Verrept, Geethika Arekatla

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Abstract INTRODUCTION In neurodegenerative dementias, the co-occurrence and interaction of Aβ, tau, other pathological lesions confound their individual contributions to neurodegeneration modulation by risk factors. METHODS We analyzed 480 post-mortem human brains (ages 50–99) using regression structural equation models assess relationships among LATE-NC, α-synuclein, age-related lesions, APOE ε4, as well effects on CA1 neuronal density, brain weight, cognitive status. RESULTS amygdala-predominant α-synuclein pathology were highly interconnected. Tau was strongest predictor global neurodegeneration, while LATE-NC primarily, but not exclusively, affected hippocampal neuron loss. Small vessel disease correlated with both ε4 mainly associated extracellular capillary Aβ. DISCUSSION Although Alzheimer’s plays a central role in degeneration, coexisting pathologies can exacerbate independently contribute it. These factors should be considered patient stratification.

Language: Английский

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