Frontotemporal dementia (FTD) is second only to Alzheimer’s disease as a cause of dementia. It is mainly sporadic but may be familial, often with a mutation (P301L) in the tau gene. Behavioural and language disturbances are common and it may be associated with parkinsonism in some cases and motor neurone disease in others. The detailed findings in an asymptomatic woman with this mutation have been described from Italy.

Two of the subject’s three brothers had developed FTD. Her one sister and the third brother were asymptomatic and neurologically and psychometrically normal at age 58 and 52 respectively and did not carry the mutation. The P301L mutation was demonstrated in the asymptomatic subject and her two affected brothers. At the age of 50 she was holding down a demanding job, leading an appropriate social life, and showed no behavioural abnormalities. She performed normally on a battery of cognitive tests with the single exception of the Verbal Fluency Test for letters in which she produced only 17 words in one minute compared with the 30 and 43 words of her two unaffected siblings. Brain CT and gross inspection of brain single photon emission computed tomography (SPECT) showed no abnormality but on SPECT with statistical parametric mapping (SPECT-SPM) there was reduced blood flow in the frontal lobes, particularly the dorsolateral frontal cortex and frontal poles and the mesial frontal cortex. SPECT-SM on the normal sister was within normal limits. The subject’s cerebrospinal fluid (CSF) contained increased levels of Aβ1-42, tau protein, and 181P-tau. (Patients with Alzheimer’s disease have high tau and low Aβ1-42 levels in CSF.)

Testing for the abnormalities found in this asymptomatic subject might improve early diagnostic accuracy in FTD and help to distinguish it from Alzheimer’s disease.