Aug 2026· Proceedings of the National Academy of Sciences of the United States of America· Vol 123· 0 citations· 83 references
Medicine
TL;DR
This work uses an adeno-associated virus-induced longitudinal macaque model of Alzheimer’s disease to examine early changes in behavior, neuronal population activity, and pathology and suggests that early disease is accompanied by a progressive loss of coordinated population activity.
Abstract
Significance In this study, we use an adeno-associated virus (AAV)-induced longitudinal macaque model of Alzheimer’s disease to examine early changes in behavior, neuronal population activity, and pathology. Our findings suggest that early disease is accompanied by a progressive loss of coordinated population activity. Rather than reflecting a uniform degradation of function, early disease progression is marked by parallel changes in the organization of neuronal populations and behavior. This work extends principles from systems and computational neuroscience to the study of neurodegenerative disease and highlights neuronal population organization as an intermediate level linking molecular pathology to behavior.
In human Alzheimer’s disease, remodeling was strongest in several deep-layer and RORB-positive excitatory populations independently associated with vulnerability, and an independently defined human depletion-associated neuronal identity instead overlapped other synaptic and calcium-signaling components of the same broa...
Sara Sejer, Magnus Møller Pedersen, Josephine Marie Boldt Lundby et al.· bioRxiv· 0 citations
In Alzheimer's disease, pathological stimuli reshape astrocyte functions, which in turn act on neurons, making astrocytes critical modulators of disease progression. A comprehensive understanding of how astrocytes dynamically shift from physiology to pathology across multiple functional domains remains to be establishe...
The results demonstrate the unique effects of nAβ toxicity on neuronal dynamics and connectivity as well as the role of key metabolic pathways within the context of a complete, intact, aging nervous system.
Dilip Yadav, Christopher W. Connor, Christopher V. Gabel· bioRxiv· 0 citations
The human brain has undergone a threefold increase in size as well as changes in cytoarchitecture and neurochemical organization since the split with the last common ancestor with chimpanzees and bonobos. These changes have likely promoted increased cognitive flexibility but may also have come at the cost of increased...
Isabel August, Sheila Steiner, Ruth Oefner et al.· Journal of Human Evolution· 0 citations
Progressive, age-dependent remodeling of motor cortex somatotopic remodeling is demonstrated in 5XFAD mice, characterized by early expansion of specific simple movement cortical sites followed by deterioration of both complex and simple motor cortical maps as disease advances.
SE Moss, Cassandra C. Wolsh, Rmii Brown et al.· bioRxiv· 0 citations
