Janssen, J-C.J.M.I.; (2006) Clinical, biochemical and neuroimaging studies in familial Alzheimer's disease. Doctoral thesis , University of London.

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Abstract

This thesis investigates several aspects of familial Alzheimer disease (FAD). The specific results of the work undertaken for this thesis were: (1) The proportion of FAD accounted for by mutations in known genes was 68% in 31 FAD families Those without mutations were ten years older and associated with APOE e4 (2) The phenotype of PSEN1 FAD was found to share an early age at onset and features broadly suggestive of AD. However the phenotype was broad and included spastic paraparesis in association with "cotton wool" plaques in PSEN1 E280G (3) Plasma amyloid P peptide was found to be a potentially useful biomarker of FAD with levels being elevated in mutations carriers compared with non-carriers, and levels in at risk subjects falling halfway between the groups (4) Cerebral atrophy in early onset AD was 2-8% (95% CI 2-3-3-3) per year which rose by 0-32% per year (0-15-0-50) (5) Pre-symptomatic medial temporal lobe atrophy in FAD at risk family members who become symptomatic was demonstrated with MRI medial temporal lobe volumes 16.6% lower in patients than controls and a higher rate of atrophy in patients than controls (6) Cerebral atrophy in FAD was shown to begin in the posterior cingulate, temporoparietal and medial temporal cortices in presymptomatic FAD patients, a finding in accordance with previous cross-sectional neuropathological studies (7) By contrast the onset and progression of cerebral atrophy in non-AD familial dementia was shown to markedly different in an presymptomatic FTLD patient with focal left frontal lobe onset reflecting the different clinical presentation (8) Cerebral atrophy in FAD was found not to progress significantly faster than sporadic AD despite a twenty year age difference between the groups.

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