Subgroups of Alzheimer's disease based on cerebrospinal fluid molecular markers.
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 Abeta(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 Abeta(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.
Iqbal
Khalid
K
New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. iqbalk@worldnet.att.net
Flory
Michael
M
Khatoon
Sabiha
S
Soininen
Hilkka
H
Pirttila
Tuula
T
Lehtovirta
Maarit
M
Alafuzoff
Irina
I
Blennow
Kaj
K
Andreasen
Niels
N
Vanmechelen
Eugeen
E
Grundke-Iqbal
Inge
I
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D015153:Blotting, Western / Q000379:methods; D016000:Cluster Analysis; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016874:Neurofibrillary Tangles / Q000473:pathology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D058225:Plaque, Amyloid / Q000473:pathology; D011180:Postmortem Changes; D025801:Ubiquitin / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; D025801:Ubiquitin; C075222:amyloid beta-protein (1-42); D016875:tau Proteins