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

• Published in: Nature neuroscience Vol. 7; no. 11; pp. 1181 - 1183
• Main Authors: Gan, Wen-Biao, Tsai, Julia, Grutzendler, Jaime, Duff, Karen
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-11-2004
• Subjects: Alzheimer's disease; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Cerebral Cortex - pathology; Diagnosis; Diagnostic Imaging - methods; Glycoproteins; In Vitro Techniques; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Transgenic; Neurites - metabolism; Neurofibrillary Tangles - metabolism; Neurons; Neurons - physiology; Physiological aspects; Plaque, Amyloid - metabolism; Presenilin-1; Risk factors; Synapses - metabolism; Synapses - pathology; Time Factors; United States
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn1335

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.