Atrophy of the hippocampal formation in early familial Alzheimer's disease. A longitudinal MRI study of at-risk members of a family with an amyloid precursor protein 717Val-Gly mutation.

The hippocampal formation (HF) is known from pathological and magnetic resonance imaging (MRI) studies to become severely atrophied in established Alzheimer's disease (AD). This study examined whether changes in the HF could also be detected in very early AD by scanning subjects at risk of developing familial AD (FAD). Five at risk members of a pedigree with the amyloid precursor protein (APP) 717 valine to glycine mutation underwent serial MRI scanning with volumetric measurement of the HF as well as neurological and neuropsychological assessments. Over a period of two years two subjects became clinically affected, a loss of up to 20% of the volume of the HF occurred in the two years over which symptoms first appeared. Asymmetrical HF atrophy was shown to have been present before the development of overt symptoms. This may have important implications for early diagnosis in AD more generally.