Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches.
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.
Molecular Neurobiology Program, Skirball Institute and Department of Neuroscience and Physiology, New York University School of Medicine, New York, New York 10016, USA.
Julia
J
Tsai
Jaime
J
Grutzendler
Karen
K
Duff
Wen-Biao
WB
Gan
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000473:pathology*; D003952:Diagnostic Imaging / Q000379:methods; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D058225:Plaque, Amyloid / Q000378:metabolism*; D053764:Presenilin-1; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor; D001426:Bacterial Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D053764:Presenilin-1; C054562:yellow fluorescent protein, Bacteria