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Subgroups of Alzheimer's disease based on cerebrospinal fluid molecular markers
Author(s) -
Iqbal Khalid,
Flory Michael,
Khatoon Sabiha,
Soininen Hilkka,
Pirttila Tuula,
Lehtovirta Maarit,
Alafuzoff Irina,
Blennow Kaj,
Andreasen Niels,
Vanmechelen Eugeen,
GrundkeIqbal Inge
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20639
Subject(s) - senile plaques , cerebrospinal fluid , disease , alzheimer's disease , pathology , dementia , medicine , degenerative disease , tauopathy , neurodegeneration
Alzheimer's disease, the most common cause of dementia, is multifactorial and heterogeneous; its diagnosis remains probable. We postulated that more than one disease mechanism yielded Alzheimer's histopathology, and that subgroups of the disease might be identified by the cerebrospinal fluid (CSF) levels of proteins associated with senile (neuritic) plaques and neurofibrillary tangles. We immunoassayed levels of tau, ubiquitin, and Aβ 1‐42 in retrospectively collected CSF samples of 468 clinically diagnosed Alzheimer's disease patients (N = 353) or non‐Alzheimer's subjects (N = 115). Latent profile analysis assigned each subject to a cluster based on the levels of these molecular markers. Alzheimer's disease was subdivided into at least five subgroups based on CSF levels of Aβ 1‐42 , tau, and ubiquitin; each subgroup presented a different clinical profile. These subgroups, which can be identified by CSF analysis, might benefit differently from different therapeutic drugs. Ann Neurol 2005;58:748–757