Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer's disease

Abstract

We assessed cerebrospinal fluid (CSF) levels of tau and other biomarkers of neurodegenerative disease. CSF tau levels vary widely in reports of frontotemporal dementia (FTD). CSF samples were assayed for tau, amyloid beta1-42 (A1-42), and the isoprostane 8,12-iso-iPF2a-VI (iP) prospectively in 64 patients with FTD, retrospectively in 26 autopsied cases with FTD or Alzheimer's disease (AD), and in 13 healthy seniors. To validate our observations in vivo, we correlated CSF tau levels with cortical atrophy in 17 FTD patients using voxel-based morphometry analyses of high-resolution magnetic resonance imaging. CSF levels of tau, Abeta1-42, and iP differed significantly in FTD compared with AD. Individual patient analyses showed that 34% of FD patients had significantly low levels of CSF tau, although this was never seen in AD. A discriminant analysis based on CSF levels of tau, Abeta1-42, and iP was able to classify 88.5% of these patients in a manner that corresponds to their clinical or autopsy diagnosis. Magnetic resonance imaging studies showed that CSF tau levels correlate significantly with right frontal and left temporal cortical atrophy, brain regions known to be atrophic in patients with autopsy-proved FTD. We conclude that CSF tau levels are significantly reduced in many patients with FTD.

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

“…-Tau proteins Increase of T-tau CSF levels was found in AD patients as well as MCI patients who will develop later an AD (Riemenschneider, Buch et al 1996;Andreasen, Minthon et al 2001;Riemenschneider, Lautenschlager et al 2002;Hansson, Zetterberg et al 2006). Measurement of T-tau levels with ELISA test (Innotest hTau Ag, Innogenetics) reveal concentrations between 150 pg/mL and 450 pg/mL in control subjects and between 300 and 1100 pg/mL in AD patients (Riemenschneider, Lautenschlager et al 2002;Grossman, Farmer et al 2005). Nevertheless, increase of T-tau CSF levels is not AD specific since it is also observed in different concentrations in CJD or even an acute stroke (Otto, Wiltfang et al 1997;Hesse, Rosengren et al 2000).…”

“…The Clinical Spectrum of Alzheimer's Disease -The Charge Toward Comprehensive Diagnostic and Therapeutic Strategies 226 in accordance with pathological heterogeneity of FTD (neuropathological tau inclusions or without tau inclusions) since existence of discordance between studies with increase of CSF T-tau levels or not (Riemenschneider, Wagenpfeil et al 2002;Grossman, Farmer et al 2005). Any biological argument does exist with T-tau CSF levels in pathologies like FTD or other tauopathies as PSP and CBD (Urakami, Wada et al 2001).…”

Validation of amyloid-β peptides in CSF diagnosis of neurodegenerative dementias

“…19,20 Nevertheless, levels of decreased Ab 1-42 and increased tau can also be found in other dementias, such as VAD, 21 DLB, 22 FTLD 23 and CJD. 24 At a sensitivity of 85% for AD detection, the diagnostic value of these biomarkers for the exclusion of non-Alzheimer dementias was therefore limited to 58%.…”

Morphometric Changes in the Episodic Memory Network and Tau Pathologic Features Correlate with Memory Performance in Patients with Mild Cognitive Impairment

“…5 It has not been tested whether these changes can be explained by levels of CSF biomarkers in AD, only in frontotemporal dementia. 13 Furthermore, the number of 4 alleles of the apolipoprotein E (APOE) gene is an established risk factor for AD 14 and is suggested to interact with A␤ to inhibit clearance or stimulate deposition of A␤, 15 enhance A␤ production, 16 and initiate cortical thinning. 17 2) How are brain morphometry, CSF biomarkers, and APOE allelic variation related to episodic memory function in MCI?…”