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Acta Neuropathologica
Published in: Acta Neuropathologica 2/2011

01-02-2011 | Original Paper

The pathological process underlying Alzheimer’s disease in individuals under thirty

Authors: Heiko Braak, Kelly Del Tredici

Published in: Acta Neuropathologica | Issue 2/2011

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Abstract

Brains of 42 individuals between the ages of 4 and 29 were examined with antibodies (AT8, 4G8) and silver stains for the presence of intraneuronal and extracellular protein aggregates associated with Alzheimer’s disease. Thirty-eight of 42 (38/42) cases displayed abnormally phosphorylated tau protein (pretangle material) in nerve cells or in portions of their cellular processes, and 41/42 individuals showed no extracellular amyloid-β protein deposition or neuritic plaques—an individual with Down syndrome was the only exception. In 16/42 cases abnormal tau was found in the transentorhinal region, and in 3/42 cases this site was Gallyas-positive for isolated NFTs (NFT stage I). Of 26 cases that lacked abnormal tau in the transentorhinal region, 4 did not show pretangle material at subcortical sites. The remaining 22 of these same 26 cases, however, had subcortical lesions confined to non-thalamic nuclei with diffuse projections to the cerebral cortex, and, remarkably, in 19/22 individuals the pretangle material was confined to the noradrenergic coeruleus/subcoeruleus complex. Assuming the pretangle alterations are not transient and do not regress, these findings may indicate that the Alzheimer’s disease-related pathological process leading to neurofibrillary tangle formation does not begin in the cerebral cortex but, rather, in select subcortical nuclei, and it may start quite early, i.e., before puberty or in early young adulthood.
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Metadata
Title
The pathological process underlying Alzheimer’s disease in individuals under thirty
Authors
Heiko Braak
Kelly Del Tredici
Publication date
01-02-2011
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 2/2011
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-010-0789-4

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