A 50-YEAR PERSPECTIVE OF A FAMILY WITH CHROMOSOME-14-LINKED ALZHEIMERS-DISEASE

A Swedish family with two generations suffering from presenile dementi a with an unusually severe Alzheimer encephalopathy was first reported in 1946. The hypothesis that the disease was inherited through a domi nant gene is strongly supported by the follow-up 50 years later of thr ee additional generations and molecular genetic findings of a novel pr esenilin-1 gene mutation in the family. The pedigree contains six case s with well-documented dementia in four consecutive generations. The A lzheimer encephalopathy was unusually severe in the three cases studie d post-mortem, with a pronounced involvement of the central grey struc tures, such as the claustrum, the nuclei around the third ventricle, t he central thalamic nuclei and the brain stem. There were no vascular lesions and little amyloid angiopathy. All six affected cases showed t he typical temporoparietal symptom pattern and other core symptoms of Alzheimer's disease, such as logoclonia, myoclonic twitchings and majo r motor seizures. Other predominant features were psychomotor slowness , increased muscular tension, a stiff stooped gait and a rapid loss of weight. The symptom pattern is convincingly explained by the consiste nt and severe involvement of cortical and central grey structures and is probably linked to the presenilin-1 gene mutation.