Acta Neuropathologica

, Volume 121, Issue 5, pp 589–595

Alzheimer’s pathogenesis: is there neuron-to-neuron propagation?


DOI: 10.1007/s00401-011-0825-z

Cite this article as:
Braak, H. & Del Tredici, K. Acta Neuropathol (2011) 121: 589. doi:10.1007/s00401-011-0825-z


There is increasing interest in the early phase of Alzheimer’s disease before severe neuronal dysfunction occurs, but it is still not known when or where in the central nervous system the underlying pathological process begins. In this review, we discuss the idea of possible disease progression from the locus coeruleus to the transentorhinal region of the cerebral cortex via neuron-to-neuron transmission and transsynaptic transport of tau protein aggregates, and we speculate that such a mechanism together with the very long prodromal period that characterizes Alzheimer’s disease may be indicative of a prion-like pathogenesis for this tauopathy. The fact that AT8-immunoreactive abnormal tau aggregates (pretangles) develop within proximal axons of noradrenergic coeruleus projection neurons in the absence of both tau lesions (pretangles, NFTs/NTs) in the transentorhinal region as well as cortical amyloid-β pathology means that currently used neuropathological stages for Alzheimer’s disease will have to be reclassified.


Alzheimer’s disease Amyloid-β Locus coeruleus Microtubules Pretangles Protein misfolding Prion diseases Staging Tau 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Clinical Neuroanatomy (Department of Neurology), Center for Clinical ResearchUniversity of UlmUlmGermany

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