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New Insights into Biological Markers of Frontotemporal Lobar Degeneration Spectrum

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In the last decade, there has been enormous progress in our understanding of Frontotemporal Lobar Degeneration (FTLD). Published clinicopathological series have clearly demonstrated an overlap between the clinical syndromes subsumed under the term frontotemporal dementia and the Progressive Supranuclear Palsy (PSP), and the Corticobasal Degeneration (CBD) syndrome. From a neuropathological point of view, two broad pathological subdivisions of FTLD are currently recognized: a) tau-positive pathology due to the accumulation of various forms of the microtubule-associated protein tau, that encompasses FTLD with Pick bodies, PSP and CBD, and b) tau-negative pathology, mainly characterised by ubiquitin/TDP-43-immunoreactive inclusions and in some cases due to Progranulin mutations.

Several biological markers in cerebrospinal fluid and in blood have been evaluated to identify monogenic forms of FTLD and to differentiate either FTLD spectrum disorders or FTLD from other neurodegenerative disorders. The proposed biomarkers are primarily related to the mechanisms underlying the accumulation of the abnormal proteins in FTLD such as Tau, TDP-43 and Progranulin. These biomarkers may support the accurate diagnosis of the specific diseases causing FTLD, can be useful in assessing efficacy during pharmacological trials, and may help in identifying new molecular targets for treatment approaches.

In this review, we summarise the most recent findings on biological markers and their usefulness in clinical practice for the diagnosis and management of FTLD.
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Keywords: Frontotemporal Lobar degeneration; biomarkers; cerebrospinal fluid; corticobasal degeneration syndrome; frontotemporal dementia; progranulin; progressive supranuclear palsy; tau

Document Type: Research Article

Affiliations: Clinica Neurologica, Universita degli Studi di Brescia, Pza Spedali Civili, 1 - 25100 Brescia, Italy.

Publication date: 2010-04-01

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