The cognitive consequences of the mutant TTR in TTR-FAP patient remain still to be elucidated.

Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an AD disorder caused by mutations of the transthyretin (TTR) gene. The mutant amyloidogenic transthyretin protein causes the systemic accumulation of amyloid fibrils in various organs, particularly in the periph eral nerve, heart, ocular vitreous and kidney.  TTR is an important protein in peripheral and central nervous system physiology, in the maintenance of normal cognitive processes during ageing, amidated neuropeptide processing and nerve regeneration.  In a transgenic mice model overexpression of TTR was positively correlated with a neuroprotective effect from the pathogenic APPsw mutation. Here, we present preliminary results of detailed cognitive investigations and CSF Aβ1–42, hTau-Ag and phospho-Tau(181P) IVD analyses of TTR-FAP patients.

Median age of the patients was 55 years (ranges 35-70). Neuropsychological test results were compatible with variable degrees of frontal dysexecutive syndrome with reduced verbal fluency and vigilance, mild impairment in abstract thinking, and working memory in four patients younger than 70 years (4/8), one of them was 35 years old. Beta amiloid 1-42 was lower than 813 pg/ml in one patient at age 72 years (1/5) and just above the cut-off value in one patient at age 53 years. Other patients (3/5) were younger than 40 years with only minimal symptoms of the disease (Stage 1). CSF analyses results are still pending in 5 patients with more advanced stage disease. Cranial MRI showed generalized cortical atrophy in four patients (4/7).

Our preliminary data showed importance of  TTR protein in cognitive functions and highlighted the importance of the close follow-up of the cognitive functions in TTR-FAP patients.