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PSEN1 (2)

PSEN1 encodes presenilin-1, a subunit of γ-secretase, the aspartyl protease responsible for Aβ generation. More than 300 mutations in PSEN1 have been reported and mutations in PSEN1 are the most common cause of early onset Alzheimer's disease.

Mutation Clinical
Phenotype		 Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change		 Research
Models		 Primary
Papers
M146L (A>C)
 Alzheimer's Disease, Pick's disease AD : Pathogenic

Neuropathology consistent with AD in multiple affected mutation carriers. Pick bodies and Lewy body pathology, as assessed by α-synuclein staining, have been noted in some cases.

Increased Aβ42, Aβ42/Aβ total, Aβ42/Aβ40 in cells and in vitro assays and decreased Aβ37/Aβ42. Impaired calcium dynamics, mitochondrial permeability, expression of synaptic and neuronal differentiation genes.

rs63750306, rs63750306 		Exon 5 Point, Missense
ATG to CTG		 18 Sherrington et al., 1995;
Sorbi et al., 1995;
Alzheimer's Disease Collaborative Group, 1995
M146L (A>T)
 Alzheimer's Disease AD : Pathogenic

Neuropathology consistent with AD. In one case, Lewy body pathology in the amygdala, cingulate gyrus, and substantia nigra. 

Increased Aβ42, Aβ42/Aβ total, Aβ42/Aβ40 in cells and in vitro assays and decreased Aβ37/Aβ42. Impaired calcium dynamics, mitochondrial permeability, expression of synaptic and neuronal differentiation genes.

rs63750306, rs63750306 		Exon 5 Point, Missense
ATG to TTG		 0 Mangone et al., 1995;
Morelli et al., 1998