A Novel Presenilin 1 Mutation (Leu166Arg) Associated With Early-Onset Alzheimer Disease

Abstract

A novel missense mutation (Leu166Arg) at an atypical site associated with early-onset Alzheimer disease has been identified in a Spanish family.

A novel presenilin 1 deletion (p.L166del) associated with early onset familial Alzheimer's disease

“…Further, this novel deletion was not detected in 100 healthy controls – suggesting that it is unlikely to represent a common, non‐pathogenic polymorphism. Mutations at this site co‐segregating with clinical disease have previously been reported [10–12] as has a deletion at codon 167 [13]. In two of the former cases, a clinical phenotype similar to our proband is described [10,12].…”

“…Mutations at this site co‐segregating with clinical disease have previously been reported [10–12] as has a deletion at codon 167 [13]. In two of the former cases, a clinical phenotype similar to our proband is described [10,12]. In the third (L166P), an aggressive onset in adolescence occurs with later spastic paraparesis [11].…”

Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Aβ 42 production

“…In addition, a FAD mutation changing leucine 166 to arginine has been identified in a Spanish family (33). To investigate this critical site of PS1 in more detail, we examined the effects of the L166 FAD mutations, as well as of several artificial mutations at this residue on APP and Notch endoproteolysis.…”

The Amyloid β-Protein Precursor and Alzheimers Disease. Therapeutic Approaches

“…Thus, an increase of Aβ42 is obtained in transgenic mice overexpressing human PS1 containing the A246E mutation and human AβPP with the Swedish mutation (K670N/M671L) [134]. There are more than 100 mutations identified in PS1, whilst few mutations have been found in PS2 [135][136][137][138][139][140][141][142][143][144][145][146][147].…”