Alzheimer's disease biomarkers: walk with deliberate haste, don't run blithely on?
Alzheimer's disease biomarkers: walk with deliberate haste, don't run blithely on?
复制标题
阿尔茨海默病生物标志物：走路时要刻意匆忙，不要轻快地奔跑？
DOI：
10.1007/s00401-013-1197-3
复制
发表时间：
2013
影响因子：
12.7
通讯作者：
Trojanowski,JohnQ
中科院分区：
文献类型：
--
作者：
Hu,WilliamT;Shaw,LeslieM;Trojanowski,JohnQ
The term biomarker originated from petroleum engineering, when Wolfgang Seifert at Chevron used it to describe the origin of hydrocarbons in petroleum. Since then, the term biomarker has evolved and even become popular in medicine and other disciplines. A quick survey of original publications indexed in PubMed containing the term “biomarker” in the title or abstract has increased 45-fold from 1994 to 2012, and the number of publications which contain “Alzheimer’s disease (AD)” and “biomarker” also increased from under 10 in 2000 to over 300 in 2013. While this is most probably an underestimate of all biomarker-related work (after all, the search term “biomarker” poorly predicts biomarker studies), the increasing use of this term in the era of title character count and abstract word count can be viewed as scientists’ interest in this topic. Compared to our colleagues focused on more accessible organ systems, clinical neuroscientists rarely have the opportunity to analyze sufficient sampling from the brain in the ante-mortem phase to elucidate the sequence of events leading to cognitive decline. We are thus often at a fork in the road where we must decide to wait until autopsy for tissue studies, or to use imperfect methods to infer time-dependent changes in living patients. These imperfect methods constitute many of the current biomarkers in use or under investigation, and this special cluster of Acta Neuropathologica has assembled a series of original papers and reviews which highlight their potential values and as well as challenges and controversies in basic and clinical research in AD to highlight the relatively rapid pace of their translation.Within Alzheimer’s disease (AD) biomarker research, much discussion has focused on the prediction of neuritic plaques and neurofibrillary tangles in keeping with the neuropathologic diagnosis for AD. We often compare ante-mortem biomarker changes to post-mortem neuropathologic changes. Using this approach, AD biomarkers will always be imperfect as only the cumulative biomarker changes across the lifetime of a subject will amount to the neuropathologic changes seen at death. Here lies an intrinsic paradox in the value of any AD biomarker: biomarker changes may correspond perfectly with neuropathologic changes early in the disease course, but our analysis is limited to comparison of ante-mortem biomarker with post-mortem neuropathologic changes. The recognition of this paradox is crucial especially when there are few longitudinal biomarker studies to associate the trajectory of biomarker changes (instead of absolute levels) towards end-of-life neuropathologic analysis. Many of the controversies in determining the sequence and topology of AD pathology also center around this paradox. That said, the goal of much biomarker research is to advance this field to the point where a panel of biomarkers of AD and related neurodegenerative diseases can replace post-mortem neuropathology studies as the ante-mortem diagnostic “gold standard”. To that end, in this special cluster, Drs. Braak, Zetterberg, Del Tredici, and Blennow directly addressed the contradictory hypotheses on the emergence of AD pathophysiology [2]. Whereas cross-sectional pathologic series have shown neurofibrillary tangles in the absence of or well before the emergence of neuritic plaques in cognitively normal young and middle-aged people who have died from non-AD related causes, cerebrospinal fluid (CSF) characterization of “AD pathology”(using levels of beta-amyloid 1–42 [Aβ42] and total Tau [t-Tau]) identifies many more cognitively normal subjects with “pathologic” Aβ42 but normal t-Tau levels than the opposite …
