The two PS1 mutation carriers with a clinical diagnosis of early-onset AD did not show the typical regional pattern of PiB retention observed in sporadic AD.
In the current letter, we expand this observation by describing an additional 15 independent families with the Ala431Glu substitution in the PSEN1 gene and conclude that this mutation is not an uncommon cause of early-onset autosomal dominant AD in persons of Mexican origin.
Presenilin-1 cases also exhibited numerous ring-like NF-positive and elongated tau-labelled dystrophic neurites, whereas these dystrophic neurite types were only abundant at the very early (pathologically aged cases) or very late stages of sporadic AD progression, respectively.
Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulation.
In our genotype-based meta-analysis, the PS-1 2/2 genotype was probably related with AD for the European sub-group (fixed effects model, OR 1.19, 95% CI 1.02-1.37, p<0.05), but there are many confusing factors between different studies.
To investigate whether known genes that cause spastic paraparesis could act as Alzheimer's disease-modifier genes, we sequenced nine spastic paraparesis genes in three Alzheimer's disease families with PSEN1 exon 9 deletions.
We now report a sporadic early-onset patient with AD, and show that this individual is a somatic mosaic for a mutation in the presenilin-1 gene, suggesting a novel molecular mechanism for AD.
Membranes from brain cortex of Alzheimer's disease patients, or from cases with presenilin 1 missense mutations, indicated no change in presenilin 1 complex mobility.