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Alzheimer's pathogenesis: is there neuron-to-neuron propagation?
Heiko Braak1, Kelly Del Tredici
1Clinical Neuroanatomy (Department of Neurology), Center for Clinical Research, University of Ulm, Ulm, Germany. heiko.braak@uni-ulm.de
Acta Neuropathologica
|April 26, 2011
Summary
Early Alzheimer's disease may start in the locus coeruleus, with tau protein aggregates spreading to the brain. This suggests a potential prion-like spread, requiring reclassification of current Alzheimer's disease staging.
Area of Science:
- Neuroscience
- Neuropathology
- Prion Diseases
Background:
- Understanding the initial site and spread of Alzheimer's disease (AD) pathology is crucial for early intervention.
- Current neuropathological staging of AD may not accurately reflect the earliest disease processes.
Purpose of the Study:
- To review and discuss the potential early pathological progression in Alzheimer's disease.
- To explore the hypothesis of prion-like pathogenesis for tauopathies in AD.
Main Methods:
- Review of existing literature on Alzheimer's disease.
- Analysis of tau protein aggregate transmission pathways.
- Discussion of neuropathological findings in early AD.
Main Results:
- Abnormal tau aggregates (pretangles) are observed in the locus coeruleus neurons early in AD.
- This occurs before tau lesions and amyloid-beta pathology are present in the transentorhinal region and cortex.
- Neuron-to-neuron transmission and transsynaptic transport of tau aggregates are proposed mechanisms.
Conclusions:
- The early pathological process in Alzheimer's disease may originate in the locus coeruleus.
- A prion-like mechanism for tauopathy spread is a plausible hypothesis for AD.
- Existing neuropathological staging for Alzheimer's disease requires reclassification based on these early findings.
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