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Review
. 2023 Jul 21;24(14):11732.
doi: 10.3390/ijms241411732.

Frontotemporal Dementia, Where Do We Stand? A Narrative Review

Annibale Antonioni  1   2 , Emanuela Maria Raho  1 , Piervito Lopriore  3 , Antonia Pia Pace  4 , Raffaela Rita Latino  5 , Martina Assogna  6   7 , Michelangelo Mancuso  3 , Daniela Gragnaniello  8 , Enrico Granieri  1 , Maura Pugliatti  1 , Francesco Di Lorenzo  7 , Giacomo Koch  7   9   10
Affiliations
Review

Frontotemporal Dementia, Where Do We Stand? A Narrative Review

Annibale Antonioni et al. Int J Mol Sci. .

Abstract

Frontotemporal dementia (FTD) is a neurodegenerative disease of growing interest, since it accounts for up to 10% of middle-age-onset dementias and entails a social, economic, and emotional burden for the patients and caregivers. It is characterised by a (at least initially) selective degeneration of the frontal and/or temporal lobe, generally leading to behavioural alterations, speech disorders, and psychiatric symptoms. Despite the recent advances, given its extreme heterogeneity, an overview that can bring together all the data currently available is still lacking. Here, we aim to provide a state of the art on the pathogenesis of this disease, starting with established findings and integrating them with more recent ones. In particular, advances in the genetics field will be examined, assessing them in relation to both the clinical manifestations and histopathological findings, as well as considering the link with other diseases, such as amyotrophic lateral sclerosis (ALS). Furthermore, the current diagnostic criteria will be explored, including neuroimaging methods, nuclear medicine investigations, and biomarkers on biological fluids. Of note, the promising information provided by neurophysiological investigations, i.e., electroencephalography and non-invasive brain stimulation techniques, concerning the alterations in brain networks and neurotransmitter systems will be reviewed. Finally, current and experimental therapies will be considered.

Keywords: C9orf72; behavioural variant; biomarkers; frontotemporal dementia (FTD); neurodegenerative dementias; non-Alzheimer’s disease dementias; primary progressive aphasias; tau.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Main FTD biomarkers and their pathomechanisms. CSF: cerebrospinal fluid; DPRs: dipeptide repeat proteins; GFAP: glial fibrillary acidic protein; GRN: progranulin; NfLs: neurofilaments; RT-QuIC: real-time quaking-induced conversion; s-TREM2: soluble fraction of protein triggering receptor expressed on myeloid cells 2; TREM2: protein triggering receptor expressed on myeloid cells 2.
Figure 2
Figure 2
Main clinical, neuropsychological, neuropathological, and neuroradiological features of FTD variants.
Figure 2
Figure 2
Main clinical, neuropsychological, neuropathological, and neuroradiological features of FTD variants.
See this image and copyright information in PMC

References

    1. Olney N.T., Spina S., Miller B.L. Frontotemporal Dementia. Neurol. Clin. 2017;35:339–374. doi: 10.1016/j.ncl.2017.01.008. - DOI - PMC - PubMed
    1. Mesulam M.M., Wieneke C., Thompson C., Rogalski E., Weintraub S. Quantitative classification of primary progressive aphasia at early and mild impairment stages. Pt 5Brain. 2012;135:1537–1553. doi: 10.1093/brain/aws080. - DOI - PMC - PubMed
    1. Brun A. Identification and Characterization of Frontal Lobe Degeneration: Historical perspective on the development of FTD. Alzheimer Dis. Assoc. Disord. 2007;21:S3–S4. doi: 10.1097/WAD.0b013e31815bf511. - DOI - PubMed
    1. Logroscino G., Piccininni M., Graff C., Hardiman O., Ludolph A.C., Moreno F., Otto M., Remes A.M., Rowe J.B., Seelaar H., et al. Incidence of Syndromes Associated with Frontotemporal Lobar Degeneration in 9 European Countries. JAMA Neurol. 2023;80:279–286. doi: 10.1001/jamaneurol.2022.5128. - DOI - PMC - PubMed
    1. Erkkinen M.G., Kim M.O., Geschwind M.D. Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases. Cold Spring Harb. Perspect. Biol. 2018;10:a033118. doi: 10.1101/cshperspect.a033118. - DOI - PMC - PubMed

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