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Nat Neurosci. 2004 Nov;7(11):1181-3. Epub 2004 Oct 10.

Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches.

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  • 1Molecular Neurobiology Program, Skirball Institute and Department of Neuroscience and Physiology, New York University School of Medicine, New York, New York 10016, USA.


Amyloid plaques are a hallmark of Alzheimer disease, but their importance in its pathogenesis is controversial. By neuronal labeling and transcranial two-photon imaging, we show in a transgenic mouse model of Alzheimer disease that dendrites passing through or near fibrillar amyloid deposits undergo spine loss and shaft atrophy, and nearby axons develop large varicosities, together leading to neurite breakage and large-scale, permanent disruption of neuronal connections. Thus, fibrillar amyloid deposition is more detrimental to neuronal circuitry than previously thought, underscoring the importance of prevention and early clearance of plaques.

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