Late‐onset behavioral variant of frontotemporal lobar degeneration versus Alzheimer's disease: Interest of cerebrospinal fluid biomarker ratios

Abstract

Introduction Cerebrospinal fluid (CSF) biomarker ratios were never evaluated in late-onset (>65 years) behavioral variant of frontotemporal lobar degeneration (bvFTLD) versus Alzheimer's disease (AD). Methods A retrospective monocentric study on 44 clinically suspected amnestic AD or bvFTLD patients with onset after 65 years and available CSF and clinical data. Results The final clinical diagnosis was AD (n = 28; 64%), late-onset bvFTLD (n = 14; 32%), and others (n = 2; 4%). Applying the CSF cutoff total-tau/Aβ 1–42 of 1.06, all the bvFTLD were in the FTLD range (<1.06, bvFTLD/FTLD), whereas the AD patients were either in the AD (>1.06, AD/AD) or in the FTLD range (<1.06, AD/FTLD); CSF biomarkers were significantly different in these three groups, but not neuroradiological features or presence of episodic memory deficit. Discussion Late-onset bvFTLD is underdiagnosed. The available CSF biomarker ratio cutoff need further improvement and overestimated late-onset bvFTLD but could potentially differentiate it from AD, notably in case of conflicting results.

Cerebrospinal fluid A beta 1–40 peptides increase in Alzheimer’s disease and are highly correlated with phospho-tau in control individuals

“…We noticed that p-tau (181) values were higher and more widely distributed in the AD population with a regression slope that was higher than in the NAD population. To document further the relationship between Aβ40 and p-tau (181) outside the context of AD, the correlation was tested in a series of clinically defined patients with multiple sclerosis [ 51 ] and FTD [ 52 ] (Fig. 4 c, d).…”

“…In this work, we had to rely only on the correlation with p-tau (181) because it is the only isoform with in vitro diagnostic (IVD) certification and has been measured in large clinical cohorts. The fact that this correlation was also present in a control population including a subgroup of well-defined FTD [ 52 ] and multiple sclerosis patients [ 51 ] raises many questions, however. It is tempting to take this relationship to confirm that Aβ peptides may induce the phosphorylation of tau, as observed both in vitro and in vivo [ 64 ].…”

Cerebrospinal fluid phospho-tau T217 outperforms T181 as a biomarker for the differential diagnosis of Alzheimer’s disease and PET amyloid-positive patient identification

“…The main CSF biomarker profiles currently used for identifying AD are decreased amyloid-beta 42 (Aβ42) levels, evaluated either alone or with respect to Aβ40 [4], and increased total and phosphorylated tau levels at threonine 181 (pT181) [3][4][5][6]. This approach, based mainly on immunoassays, can be used to discriminate between AD and non-AD pathologies [7][8][9] [10] and to detect the AD process many years prior to the onset of cognitive symptoms and complaints [7,11]. However, changes in the total CSF and pT181 tau levels are not entirely specific to AD.…”

“…However, changes in the total CSF and pT181 tau levels are not entirely specific to AD. They are sometimes observed in other tauopathies, such as progressive supranuclear palsy (PSP) [8] and frontotemporal lobar degeneration (FTLD) [9], as well as dementia of other kinds, where they also reflect neurodegenerative processes. Brain studies on AD have shown the presence of many hyperphosphorylated tau sites [12][13][14][15] which might promote tau aggregation and the formation of NFT [16,17].…”

Relevance of Aβ42/40 Ratio for Detection of Alzheimer Disease Pathology in Clinical Routine: The PLMR Scale

“…Cerebrospinal fluid (CSF) protein biomarkers are nowadays included in guidelines of the National Institute of Aging-Alzheimer’s Association (NIA-AA) and the International Working Group 2 to diagnose Alzheimer’s disease (AD) in clinical research settings ( McKhann et al, 2011 ; Dubois et al, 2014 ). CSF Aβ42, tau, and/or phosphorylated tau on Threonine 181 [ptau(181)] are validated to identify AD pathology in an early phase of the disease and for differential diagnosis ( Andreasen et al, 2001 ; Engelborghs et al, 2008 ; Le Bastard et al, 2010 ; Gabelle et al, 2011 ; Schoonenboom et al, 2012 ; Marelli et al, 2015 ). Those biomarkers have been progressively integrated in daily clinical practice ( Gabelle et al, 2013 ; Molinuevo et al, 2014 ; Mouton-Liger et al, 2014 ; Troussiere et al, 2014 ; Blennow et al, 2015 ; Lewczuk et al, 2015a ; Paquet et al, 2016 ), however, the interpretation of results needs expertise and caution.…”