Original Research ARTICLE
The Use Of Biomarkers And Genetic Screening To Diagnose Frontotemporal Dementia: Evidence And Clinical Implications
- 1Center for Molecular Neurology, University of Antwerp, Belgium
- 2Institute Born-Bunge (IBB), Belgium
- 3University of Antwerp, Belgium
- 4Vrije University Brussel, Belgium
Within the wide range of neurodegenerative brain diseases, the differential diagnosis of frontotemporal dementia (FTD) frequently poses a challenge. Often, signs and symptoms are not characteristic of the disease and may instead reflect atypical presentations. Consequently, the use of disease biomarkers is of importance to correctly identify the patients..
Here, we describe how neuropsychological characteristics, neuroimaging and neurochemical biomarkers and screening for causal gene mutations can be used to differentiate FTD from other neurodegenerative diseases as well as to distinguish between FTD subtypes. Summarizing current evidence, we propose a stepwise approach in the diagnostic evaluation.
Clinical consensus criteria that take into account a full neuropsychological examination have relatively good accuracy (sensitivity [se] 75-95%, specificity [sp] 82-95%) to diagnose FTD, although misdiagnosis (mostly AD) is common. Structural brain MRI (se 70-94%, sp 89-99%) and FDG PET (se 47-90%, sp 68-98%) or SPECT (se 36-100%, sp 41-100%) brain scans greatly increase diagnostic accuracy, showing greater involvement of frontal and anterior temporal lobes, with sparing of hippocampi and medial temporal lobes. If these results are inconclusive, we suggest detecting amyloid and tau cerebrospinal fluid (CSF) biomarkers that can indicate the presence of AD with good accuracy (se 74-100%, sp 82-97%). The use of P-tau181 and the Aβ1–42/ Aβ1–40 ratio significantly increases the accuracy of correctly identifying FTD vs AD. Alternatively, an amyloid brain PET scan can be performed to differentiate FTD from AD.
When autosomal dominant inheritance is suspected, or in early onset dementia, mutation screening of causal genes is indicated and may also be offered to at-risk family members. We have summarized genotype-phenotype correlations for several genes that are known to cause familial frontotemporal lobar degeneration (FTLD), which is the neuropathological substrate of FTD. The genes most commonly associated with this disease (C9orf72, MAPT, GRN, TBK1) are discussed, as well as some less frequent ones (CHMP2B, VCP).
Several other techniques, such as diffusion tensor imaging, tau PET imaging and measuring serum neurofilament levels, show promise for future implementation as diagnostic biomarkers.
Keywords: Dementia, Fronto Temporal Dementia, Alzheimer, biomarker, Genetics, Cerebrospinal Fluid – CSF, MRI
Received: 10 Feb 2019;
Accepted: 08 Jul 2019.
Edited by:Alberto Lleo, Hospital de la Santa Creu i Sant Pau, Spain
Reviewed by:Luisa Benussi, Centro San Giovanni di Dio Fatebenefratelli (IRCCS), Italy
Martin Ingelsson, Uppsala University, Sweden
Copyright: © 2019 Gossye, Van Broeckhoven and Engelborghs. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Sebastiaan Engelborghs, University of Antwerp, Antwerp, Belgium, Sebastiaan.Engelborghs@uantwerpen.be