Investigations

Investigations

Genetic testing
See the section on Genetics for more details on this.

For people who have symptoms and have bvFTD we recommend offering genetic testing to all people. The risk of finding a genetic mutation is high if a family history is present, but is around 10% even when there is no family history. Genetic testing is usually performed as specialist centres.

Family members who do not have symptoms can undergo presymptomatic genetic testing at a specialist genetics clinic. See the page on Genetic FTD and living at-risk.

Blood tests and lumbar punctures
Taking a blood sample for serum or plasma, or performing a spinal tap for cerebrospinal fluid or CSF allows biological markers, or biomarkers, to be measured. Our research is focused on developing new biomarkers for clinical trials but we hope that some of these may be used in the clinic as well in the future. For a recent review of fluid biomarkers in FTD read this paper from our team.

One blood marker that is used in some clinics is the serum or plasma progranulin level. A low level indicates with very high likelihood the presence of a progranulin mutation. The absolute cut-off is not completely clear but using the common Adipogen assay most groups use a cut-off between 61 and 70ng/ml.

At the moment there are no other blood biomarkers of FTD used in clinic. However, a marker called neurofilament light chain or NfL has been shown to be abnormal in FTD and predicts how quickly the disease will progress in most forms of FTD. It is likely this will enter clinical practice in the years to come.

CSF markers currently used in clinic include total tau, phospho-tau and beta-amyloid 42. These markers change in people with underlying Alzheimer’s disease pathology including atypical forms such as the majority of people with lvPPA. A raised total tau and phospho-tau, and a decreased beta-amyloid 42 are together a sign of Alzheimer’s disease pathology. Some centres use a total tau: beta-amyloid 42 ratio of more than 1 as their marker.

A specific CSF marker of C9orf72 expansions called poly(GP) dipeptide repeat proteins is likely to be in clinical use in the next few years.

Other CSF markers including synaptic, inflammatory, and lysosomal measures are under investigation in FTD but are not yet in clinical practice.