Duyckaerts C, Braak H, Brion JP, Buée L, Del Tredici K, Goedert M, Halliday G, Neumann M, Spillantini MG, Tolnay M, Uchihara T. PART is part of Alzheimer disease. Acta Neuropathol. 2015 May;129(5):749-56. Epub 2015 Jan 28 PubMed.
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University of Kentucky
Duyckaerts et al. raise a number of questions. A comprehensive commentary on this paper from a large group of coauthors, including myself, is currently under review at Acta Neuropathologica. For now, speaking only for myself, and leaving aside nomenclature, I will touch on some basic issues.
Professor Heiko Braak and his colleagues, studying one of the largest and highest-quality single-center brain banks in the world, have published, in multiple peer-reviewed journals, data establishing the following fundamentally important points:
1. Every single human who lives long enough will have some neurofibrillary tangles (NFTs) in the medial temporal lobe (Braak stage >0) by their early 60s.
2. Many nonagenarians and—more importantly—20 percent or so of centenarians die without brain amyloid.
See Braak et al., 2011, and we have data that support this strongly as well.
So what does that mean?
Only about 1 percent of people live to 100. This is the very end of humans’ genetically programmed aging spectrum. The idea that those 20 percent of centenarians with NFTs but no amyloid will eventually develop AD (the plaque and tangle disease) is specious. The fundamental, very straightforward conclusion of these data is that the inevitable appearance of medial temporal lobe NFTs is not necessarily a precursor of AD, and—importantly—there are genetic and/or environmental factors that can prevent AD (amyloid plaques plus many tangles) from occurring.
A separate and important issue is: Are there genetic and/or environmental factors that could attenuate the medial temporal lobe NFTs?
References:
Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011 Nov;70(11):960-9. PubMed.
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