CSF biomarkers for Alzheimer's Disease: levels of beta-amyloid, tau, phosphorylated tau relate to clinical symptoms and survival.
Cerebrospinal fluid (CSF) samples from 21 patients with a clinical diagnosis of Alzheimer's disease (AD) participating in a 5-year treatment study with the choline esterase inhibitor tacrin were retrospectively analyzed for the contents of beta-amyloid (Abeta42), total tau (T-tau) and phosphorylated tau (P-tau). A significant positive correlation between the level of P-tau and the number of symptoms according to the DSM-IV criteria (p = 0.041) and the NINCDS-ADRDA (p = 0.029) was observed (i.e. higher levels were found in cases with more symptoms). A significant positive correlation between T-tau, P-tau and ADAS-cog score was identified (i.e. higher levels were found with more severe cognitive dysfunction). Patients who died during the 5-year follow-up had significantly lower levels of Abeta42 (p = 0.011) than those who were still alive. Patients who had died in a 6-year follow-up had significantly lower levels of Abeta42 (p = 0.034) and higher levels of T-tau (p = 0.041) than patients still alive.


CONCLUSIONS
CSF biomarkers do aid the clinical diagnosis of AD. Increased levels of P-tau and T-tau are possible markers for severity and abundance of symptoms in AD. Low levels of Abeta42 may indicate a higher risk of early death in AD.
Wallin
A K
AK
Department of Psychiatry, Neuropsychiatric Clinic, Malmö University Hospital, Malmö, Sweden. asa.k.wallin@skane.se
Blennow
K
K
Andreasen
N
N
Minthon
L
L
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid*; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D011379:Prognosis; D012016:Reference Values; D012189:Retrospective Studies; D012306:Risk; D013223:Statistics as Topic; D016019:Survival Analysis; D013619:Tacrine / Q000627:therapeutic use; D016875:tau Proteins
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D013619:Tacrine