CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease.

TitleCSF biomarkers of Alzheimer disease in HIV-associated neurologic disease.
Publication TypeJournal Article
Year of Publication2009
AuthorsClifford, DB, Fagan, AM, Holtzman, DM, Morris, JC, Teshome, M, Shah, AR, Kauwe, JSK
JournalNeurology
Volume73
Issue23
Pagination1982-7
Date Published2009 Dec 08
ISSN1526-632X
KeywordsAdult, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, CHARTER, Cohort Studies, External, HIV Infections, Humans, Middle Aged, Nervous System Diseases, tau Proteins
Abstract

BACKGROUND: HIV-associated neurologic disorders (HAND) continue to develop in many patients with HIV. CSF amyloid measurements in HAND have been reported to be similar to those in dementia of the Alzheimer type (DAT). Confirmatory evaluation of this finding in carefully evaluated subjects is needed.METHODS: CSF specimens were obtained from subjects clinically categorized with normal cognition from the general population, HIV+ subjects with normal cognition, HIV+ subjects with impaired cognition, or presumed HIV- subjects with mild DAT. CSF measurements of beta-amyloid((1-42)) (Abeta42), beta-amyloid((1-40)) (Abeta40), total tau (t-tau), and phosphorylated tau (p-tau181) were performed.RESULTS: CSF Abeta42 measured in 49 HAND subjects had a median level of 501 pg/mL, which was lower than that of 50 controls of similar age who had median of 686 pg/mL (p < 0.0001) or 21 HIV+ subjects without cognitive impairment who had median of 716 pg/mL (p < 0.003). HAND subjects had similar CSF Abeta42 to 68 subjects with mild DAT. There was no difference of CSF Abeta40 between the groups. Tau and p-tau181 was elevated in DAT, but slightly lower than control in both HIV+ groups.CONCLUSIONS: beta-Amyloid((1-42)) (Abeta42) measurements in CSF of cognitively impaired patients with HIV are similar to those in patients with mild dementia of the Alzheimer type (DAT). Normal or slightly depressed CSF tau and p-tau181 measurements distinguish these patients with HIV-associated neurologic disorders (HAND) from patients with DAT. Further evaluation of amyloid metabolism in patients with HIV cognitive disorder is needed to understand the implications of depressed CSF Abeta42 in the setting of HAND.

DOI10.1212/WNL.0b013e3181c5b445
Alternate JournalNeurology
PubMed ID19907013
PubMed Central IDPMC2790234
Grant ListP50 AG05681 / AG / NIA NIH HHS / United States
MH 22005 / MH / NIMH NIH HHS / United States
P01 AG026276 / AG / NIA NIH HHS / United States
R24MH59724 / MH / NIMH NIH HHS / United States
P50 AG005681 / AG / NIA NIH HHS / United States
R24NS45491 / NS / NINDS NIH HHS / United States
P01 AG03991 / AG / NIA NIH HHS / United States
MH05745 / MH / NIMH NIH HHS / United States
U01 MH083545 / MH / NIMH NIH HHS / United States
NS32228 / NS / NINDS NIH HHS / United States
NS38841 / NS / NINDS NIH HHS / United States