Background: Frontotemporal Dementia (FTD) is a neurodegenerative disorder which asymmetrically
affects the frontotemporal lobe, characterized by behavioural abnormalities, language impairment, and
deficits of executive functions. Genetic studies identified mutations causing the disease, namely Microtubule
Associated Protein Tau (MAPT), Granulin (GRN) and chromosome 9 open reading frame 72 (C9orf72) mutations,
which contributed to elucidate the molecular pathways involved in brain depositions of either Tau or
TAR DNA-binding protein 43 (TDP43) inclusions. However, in the majority of sporadic FTD patients, the
mechanisms triggering Tau or TDP43 protein deposition are still to be uncovered.
Objective: We aimed to present an extensive evaluation of literature data on immune homeostasis in FTD, in
order to provide potentially evidence-based approaches for a disease still orphan of any treatment.
Methods: A structured search of bibliographic databases from peer-reviewed literature was pursued focusing
on autoimmunity in the brain and FTD.
Results: One-hundred-fourteen papers were included in this review. The majority of studies (32) were represented
by extensive literature revision on immunity, central nervous system (CNS) and autoimmunity; neuroimaging
papers (11) in autoimmune diseases were evaluated, and immunomodulatory approaches (25) were
revised. Six papers were found specifically related to FTD and autoimmune hypothesis, the other papers
referring to current state of art on FTD.
Conclusion: Overall this review contribute to expand the knowledge of a possible immune hypothesis in
FTD, suggesting therapeutic perspectives in autoimmune related neurodegeneration, to reduce or revert the