Stages of the pathologic process in alzheimer disease: Age categories from 1 to 100 years

Braak, Heiko, Thal, Dietmar R., Ghebremedhin, Estifanos and Del Tredici, Kelly (2011) Stages of the pathologic process in alzheimer disease: Age categories from 1 to 100 years. Journal of Neuropathology and Experimental Neurology, 70 11: 960-969. doi:10.1097/NEN.0b013e318232a379

Author Braak, Heiko
Thal, Dietmar R.
Ghebremedhin, Estifanos
Del Tredici, Kelly
Title Stages of the pathologic process in alzheimer disease: Age categories from 1 to 100 years
Journal name Journal of Neuropathology and Experimental Neurology   Check publisher's open access policy
ISSN 0022-3069
Publication date 2011-11-01
Sub-type Article (original research)
DOI 10.1097/NEN.0b013e318232a379
Open Access Status Not yet assessed
Volume 70
Issue 11
Start page 960
End page 969
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
Two thousand three hundred and thirty two nonselected brains from 1- to 100-year-old individuals were examined using immunocytochemistry (AT8) and Gallyas silver staining for abnormal tau; immunocytochemistry (4G8) and Campbell-Switzer staining were used for the detection of[beta]-amyloid. A total of 342 cases was negative in the Gallyas stain but when restaged for AT8 only 10 were immunonegative. Fifty-eight cases had subcortical tau predominantly in the locus coeruleus, but there was no abnormal cortical tau (subcortical Stages a-c). Cortical involvement (abnormal tau in neurites) was identified first in the transentorhinal region (Stage 1a, 38 cases). Transentorhinal pyramidal cells displayed pretangle material (Stage 1b, 236 cases). Pretangles gradually became argyrophilic neurofibrillary tangles (NFTs) that progressed in parallel with NFT Stages I to VI. Pretangles restricted to subcortical sites were seen chiefly at younger ages. Of the total cases, 1,031 (44.2%) had [beta]-amyloid plaques. The first plaques occurred in the neocortex after the onset of tauopathy in the brainstem. Plaques generally developed in the 40s in 4% of all cases, culminating in their tenth decade (75%). [beta]-amyloid plaques and NFTs were significantly correlated (p < 0.0001). These data suggest that tauopathy associated with sporadic Alzheimer disease may begin earlier than previously thought and possibly in the lower brainstem rather than in the transentorhinal region.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Biomedical Sciences Publications
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Created: Fri, 21 Oct 2011, 19:57:12 EST by Bacsweet Kaur on behalf of School of Biomedical Sciences