Presenilin-2 (PSEN2) is one of two highly homologous presenilin genes expressed in vertebrates. Presenilin-1 (PSEN1) has been more extensively studied in Alzheimer’s research because fewer mutations in PSEN2 are known. Mutations in the presenilin genes are the most common cause of familial Alzheimer’s disease, with more than 150 total ...

The gene PSEN2 encodes presenilin-2, a subunit of γ-secretase, the aspartyl protease responsible for Aβ generation. Missense mutations in PSEN2 are a rare cause of early onset Alzheimer's disease. PDF (1.21 MB)

Feb 24, 2025 · The N141I mutation in PSEN2: implications for the quintessential case of Alzheimer disease. Arch Neurol. 2010 May;67(5):631-3. PubMed. Müller U, Winter P, Graeber MB. Alois Alzheimer's case, Auguste D., did not carry the N141I mutation in PSEN2 characteristic of Alzheimer disease in Volga Germans. Arch Neurol. 2011 Sep;68(9):1210-1, author ...

Jul 1, 2024 · PSEN2 Mutation Spectrum and Novel Functionally Validated Mutations in Alzheimer's Disease: Data from PUMCH Dementia Cohort. J Alzheimers Dis. 2022;87(4):1549-1556. PubMed. Liu C, Cong L, Zhu M, Wang Y, Tang S, Han X, Zhang Q, Tian N, Liu K, Liang X, Fa W, Wang N, Hou T, Du Y.

May 23, 2024 · Consistent with these findings, computer simulations of the structure and function of PSEN2 predicted this variant increases the size of the active site pocket which is expected to increase substrate diffusion resulting in increased Aβ42 and decreased Aβ40 production (Soto-Ospina et al., 2021). Moreover, the mutation's PHRED-scaled CADD score ...

May 23, 2024 · M239I was the third missense mutation in PSEN2 to be associated with Alzheimer's disease. Reported first in an Italian family in 2000 ( Finckh et al., 2000 ), it has since been identified in two additional Italian families, a Brazilian family of European ancestry, and a Chinese individual.

Feb 22, 2022 · Similarly, when co-transfected with APP carrying the Swedish mutation, D439A-PSEN2 did not affect Aβ42 levels or the Aβ42/Aβ40 ratio (Walker et al., 2005). However, a subsequent study using mouse neuroblastoma cells lacking endogenous PSEN1 and PSEN2, and expressing APP695 and the PSEN2 D439A mutant, resulted in decreased Aβ40 secretion …

Feb 22, 2022 · PSEN1, PSEN2, and APP mutations in 404 Chinese pedigrees with familial Alzheimer's disease. Alzheimers Dement. 2020 Jan;16(1):178-191. PubMed. Hsu JL, Lin CH, Chen PL, Lin KJ, Chen TF. Genetic study of young-onset dementia using targeted gene panel sequencing in Taiwan. Am J Med Genet B Neuropsychiatr Genet. 2021 Mar;186(2):67-76.

APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med. 2017 Mar;14(3):e1002270. Epub 2017 Mar 28 PubMed. Walker ES, Martinez M, Brunkan AL, Goate A.

Dec 20, 2024 · When PSEN2 is missing entirely, a build-up of β-CTF is likely the prime instigator. Without PSEN2. When PSEN2 is mutated or deleted, endolysosomal trafficking defects and Aβ accumulation derail the proper trafficking of synaptic vesicles and receptors (top). This impairs synaptic signaling and working memory (bottom left).