Phosphorylated tau 231, memory decline and medial temporal atrophy in normal elders.
Little is known whether cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) can predict both memory decline and associated longitudinal medial temporal lobe (MTL) gray matter (GM) reductions in cognitively healthy individuals. Fifty-seven normal elderly subjects received comprehensive evaluation at baseline and 2 years later. The baseline phosphorylated tau(231) (p-tau(231)), total tau, the amyloid beta (Aβ) Aβ42/Aβ40, t-tau/Aβ42 and p-tau(231)/Aβ42 ratios were examined as predictors of memory change and reductions in the global and MTL GM, determined from T1-weighted MRI. Twenty out of 57 participants experienced reduced memory performance at follow-up. The group with decreased memory performance showed higher baseline p-tau(231) (Z=-2.2, p=0.03), lower Aβ42/Aβ40 (t=-2.2 [55], p=0.04) and greater longitudinal MTL GM reductions (t([52])=-2.70, p=0.01). Higher baseline p-tau(231) was also associated with the absolute decrease in memory scores (rho=-0.30, p=0.02) and with longitudinal MTL GM reduction (F([2,52])=4.4, p=0.04, age corrected). Our results indicate that in normal individuals, elevated p-tau(231), a marker of neurofibrillary pathology is related to both a decrease in declarative memory and progressive atrophy of the MTL, suggesting its diagnostic potential in preclinical stage.
Department of Psychiatry, New York University School of Medicine, Center of Excellence on Aging, Center for Brain Health, 145 East 32nd Street, 5th floor, New York, NY 10016, USA. Lidia.Glodzik-Sobanska@nyumc.org
Lidia
L
Glodzik
Susan
S
de Santi
Wai Hon
WH
Tsui
Lisa
L
Mosconi
Raymond
R
Zinkowski
Elizabeth
E
Pirraglia
Hui Yu
HY
Wang
Yi
Y
Li
Kenneth E
KE
Rich
Henrik
H
Zetterberg
Kaj
K
Blennow
Pankaj
P
Mehta
Mony J
MJ
de Leon
D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008569:Memory Disorders / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D010766:Phosphorylation / Q000502:physiology; D013702:Temporal Lobe / Q000473:pathology*; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism*
D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins