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Microtubular reorganization and dendritic growth response in Alzheimer's disease
A C McKee1, N W Kowall, K S Kosik
1Department of Neuropathology, Massachusetts General Hospital, Boston 02114.
Abstract:
Cytoskeletal disruption is a key pathological feature of Alzheimer's disease (AD). We used refined immunocytochemical techniques to define the range of abnormalities affecting the microtubule system in AD hippocampus. Minimal tau and tubulin immunoreactivity was granular and accumulated in otherwise normal neuronal perikarya. As tau-reactive neurofibrillary tangles formed, granular tau and tubulin staining diminished, and ubiquitin reactivity developed. In regions of high neurofibrillary tangle density, microtubule-associated protein 2 (MAP2) histochemical features of remaining nontangled neurons included apical dendritic degeneration with proliferation of basal dendrites. In addition to perisomatic dendritic proliferation, there was massive sprouting of tau-immunoreactive distal dystrophic neurites. Sprouting proximal dendrites and dystrophic neurites often demonstrated growth-cone-like lamellipodia and filopodia. Degeneration of the perisomatic proliferating dendrites was characterized by the accumulation of fibrillar tau immunoreactivity. The colocalization of MAP2 and tau in growth structures recapitulated their codistribution in developing neurites. The data suggest that extensive plasticity and growth response occur in tandem with neuronal degeneration in AD, and that reorganization of the cytoskeletal microtubule system may underlie these proliferative changes.
Insights
Alzheimer's disease (AD) involves cytoskeletal changes. Neurons show both degeneration and surprising growth responses, with sprouting dendrites and neurites, suggesting complex plasticity during AD progression.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Cytoskeletal disruption is a hallmark of Alzheimer's disease (AD).
- The microtubule system is significantly affected in AD pathology.
- Understanding these changes is crucial for AD research.
Purpose of the Study:
- To investigate the detailed abnormalities of the microtubule system in the hippocampus of Alzheimer's disease patients.
- To characterize the interplay between neuronal degeneration and growth responses in AD.
Main Methods:
- Utilized refined immunocytochemical techniques.
- Examined tau, tubulin, ubiquitin, and microtubule-associated protein 2 (MAP2) immunoreactivity in AD hippocampus.
- Analyzed neuronal perikarya, neurofibrillary tangles, and dendritic structures.
Main Results:
- Early AD shows granular tau and tubulin accumulation in neurons.
- Neurofibrillary tangle formation correlates with diminished granular staining and increased ubiquitin.
- Non-tangled neurons exhibit dendritic degeneration and sprouting, with growth-cone-like structures containing MAP2 and tau.
Conclusions:
- Alzheimer's disease involves both neuronal degeneration and significant plasticity.
- Reorganization of the microtubule system underlies proliferative changes observed in AD neurons.
- These findings highlight a complex cellular response during AD pathogenesis.