Frontotemporal lobar degeneration

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A human brain showing frontotemporal lobar degeneration causing frontotemporal dementia.

Frontotemporal lobar degeneration (FTLD) is a form of dementia. In the over 65 age group it is probably the fourth most common type of dementia after Alzheimer's disease, dementia with Lewy bodies and vascular dementia. In the below 65 age group it is the second most common cause after Alzheimer's disease.

There are three clinical variants of FTLD:

There are a number of possible pathological findings at post-mortem:

tau inclusions (either with Pick bodies or without)
ubiquitin positive (tau-negative) inclusions - these ubiquitinated inclusions have recently been found to be a protein called TDP-43. There are (at least) three subtypes of this type of pathology. Mackenzie et al describe the following: type 1 with intranuclear inclusions; type 2 with neurites predominantly and type 3 with cytoplasmic inclusions predominantly.
dementia lacking distinctive histology (DLDH)

Many cases (possibly up to 50%) of FTLD are genetic rather than sporadic. Mutations in the Tau gene (on chromosome 17 - known as MAPT or Microtubule Associated Protein Tau) can cause FTLD and there are over 30 known mutations at present. A series of new mutations associated with FTLD has been recently described in the progranulin gene which is remarkably also on chromosome 17. Patients with progranulin mutations have ubiquitin positive, tau negative pathology at post-mortem. Progranulin had previously been associated with tumorgenesis, but when overproduced, whereas the mutations seen in the progranulin gene associated with FTLD suggests a deficit in progranulin may be the problem. Further research will need to be done to determine the clinical relavance of progranulin in FTLD.

[edit] References

Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF. "Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria." 'Neurology' (1998) 51(6):1546-54. Available: [1]