PET STUDY IN SUBJECTS FROM 2 ITALIAN FAD FAMILIES WITH APP717 VAL TO ILEU MUTATION

Cerebral glucose metabolism was investigated with 2-[F-18]-fluoro-2-de oxy-D-glucose ([F-18]FDG) and positron emission tomography (PET) in se wn members belonging to two Italian families with familial Alzheimer's disease (FAD) and APP717 Val to Ileu mutation, The aim of the study w as to identify the pattern of cerebral hypometabolism in the affected patients and the possible occurrence of brain metabolic changes in the APP mutated subjects. The two patients with FAD, when compared with n ormal age matched controls, showed a severe bilateral hypometabolism i n parietal and temporal regions, as well as in the prefrontal areas, w hich were more affected on the left side, Subcortical thalamic structu res were also involved in one patient. In a comparison with a group of patients with sporadic AD, the most affected cerebral areas in the FA D patients were the prefrontal regions and the thalamus, bilaterally. One of the four mutated subjects, with an age close to the family age of disease onset, in a comparison with normals, showed metabolic reduc tions in the right thalamus, in the left dorsolateral frontal cortex a nd, bilaterally, in the frontal orbital regions, This regional brain h ypometabolism was present in a preclinical phase, 1 year before the on set of dementia. In the three younger subjects carrying the mutation, a metabolic reduction was detected in the thalamus, bilaterally. These results demonstrate that a pattern of cerebral hypometabolism involvi ng cortical and subcortical structures is present in FAD patients with APP717 Val to Ileu mutation. Cerebral hypometabolism may occur in pre -symptomatic and young asymptomatic APP717 mutated FAD subjects and it ran be detected by a highly sensitive procedure such as PET.