Open AccessNovel CSF biomarkers to discriminate FTLD and its pathological subtypes
Author(s) -
del Campo Marta,
Galimberti Daniela,
Elias Naura,
Boonkamp Lynn,
Pijnenburg Yolande A.,
Swieten John C.,
Watts Kelly,
Paciotti Silvia,
Beccari Tommaso,
Hu William,
Teunissen Charlotte E.
Publication year - 2018
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.629
Subject(s) - frontotemporal lobar degeneration , biomarker , medicine , dementia , pathological , pathology , tau protein , cerebrospinal fluid , cohort , frontotemporal dementia , alzheimer's disease , disease , biology , biochemistry
Objective Frontotemporal lobar degeneration ( FTLD ) is the second most prevalent dementia in young patients and is characterized by the presence of two main protein aggregates in the brain, tau ( FTLD ‐Tau) or TDP 43 ( FTLD ‐ TDP ), which likely require distinct pharmacological therapy. However, specific diagnosis of FTLD and its subtypes remains challenging due to largely overlapping clinical phenotypes. Here, we aimed to assess the clinical performance of novel cerebrospinal fluid ( CSF ) biomarkers for discrimination of FTLD and its pathological subtypes. Methods YKL 40, FABP 4, MFG ‐E8, and the activities of catalase and specific lysosomal enzymes were analyzed in patients with FTLD ‐ TDP ( n = 30), FTLD ‐Tau ( n = 20), AD ( n = 30), DLB ( n = 29), and nondemented controls ( n = 29) obtained from two different centers. Models were validated in an independent CSF cohort ( n = 188). Results YKL 40 and catalase activity were increased in FTLD ‐ TDP cases compared to controls. YKL 40 levels were also higher in FTLD ‐ TDP compared to FTLD ‐Tau. We identified biomarker models able to discriminate FTLD from nondemented controls ( MFG ‐E8, tT au, and A β 42 ; 78% sensitivity and 83% specificity) and non‐ FTLD dementia ( YKL 40, pT au, p/ tT au ratio, and age; 90% sensitivity, 78% specificity), which were validated in an independent cohort. In addition, we identified a biomarker model differentiating FTLD ‐ TDP from FTLD ‐Tau ( YKL 40, MFGE ‐8, β HexA together with β HexA/ tH ex and p/ tT au ratios and age) with 80% sensitivity and 82% specificity. Interpretation This study identifies CSF protein signatures distinguishing FTLD and the two main pathological subtypes with optimal accuracy (specificity/sensitivity > 80%). Validation of these models may allow appropriate selection of cases for clinical trials targeting the accumulation of Tau or TDP 43, thereby increasing their efficiency and facilitating the development of successful therapies.