Neuropathologic and molecular studies in brains of carriers of the PSEN1 p.A396T mutation or other PSEN1 or PSEN2 mutations associated with the coexistence of DLBD and AD are needed to clarify whether tau and α-synuclein proteinopathies occur independently or whether a relationship exists between α-synuclein and tau that might explain the mechanisms of coaggregation.
Neuropathologic and molecular studies in brains of carriers of the PSEN1 p.A396T mutation or other PSEN1 or PSEN2 mutations associated with the coexistence of DLBD and AD are needed to clarify whether tau and α-synuclein proteinopathies occur independently or whether a relationship exists between α-synuclein and tau that might explain the mechanisms of coaggregation.
We identified two novel mutations of <i>PSEN1</i> (Y256N and H214R) in samples from these families, and a <i>de novo</i> mutation of <i>PSEN1</i> (G206V) in a patient with very early-onset sporadic Alzheimer's disease.
PSEN1 p.L226R was found in an early-onset AD (EOAD) family characterized by language impairment at disease onset, a novel probably pathogenetic variant (p.D534H) was identified in a frontal-temporal dementia gene, TANK-binding kinase 1 (TBK1) with a typical AD phenotype in a late-onset AD (LOAD) family, and a PSEN2p.H169N mutation and two benign MAPT (p.Q230R and p.V48L) mutations were detected in three EOAD patients.
PSEN1 p.L226R was found in an early-onset AD (EOAD) family characterized by language impairment at disease onset, a novel probably pathogenetic variant (p.D534H) was identified in a frontal-temporal dementia gene, TANK-binding kinase 1 (TBK1) with a typical AD phenotype in a late-onset AD (LOAD) family, and a PSEN2p.H169N mutation and two benign MAPT (p.Q230R and p.V48L) mutations were detected in three EOAD patients.
We identified two novel mutations of <i>PSEN1</i> (Y256N and H214R) in samples from these families, and a <i>de novo</i> mutation of <i>PSEN1</i> (G206V) in a patient with very early-onset sporadic Alzheimer's disease.
In addition, a heterozygous p.Arg71Trp mutation in PSEN2 with an uncertain pathogenic nature was identified in a patient with neuropathologically confirmed AD.
We identified two novel mutations of <i>PSEN1</i> (Y256N and H214R) in samples from these families, and a <i>de novo</i> mutation of <i>PSEN1</i> (G206V) in a patient with very early-onset sporadic Alzheimer's disease.
PSEN1 p.L226R was found in an early-onset AD (EOAD) family characterized by language impairment at disease onset, a novel probably pathogenetic variant (p.D534H) was identified in a frontal-temporal dementia gene, TANK-binding kinase 1 (TBK1) with a typical AD phenotype in a late-onset AD (LOAD) family, and a PSEN2p.H169N mutation and two benign MAPT (p.Q230R and p.V48L) mutations were detected in three EOAD patients.
PSEN1 p.L226R was found in an early-onset AD (EOAD) family characterized by language impairment at disease onset, a novel probably pathogenetic variant (p.D534H) was identified in a frontal-temporal dementia gene, TANK-binding kinase 1 (TBK1) with a typical AD phenotype in a late-onset AD (LOAD) family, and a PSEN2p.H169N mutation and two benign MAPT (p.Q230R and p.V48L) mutations were detected in three EOAD patients.
Dermal fibroblasts were obtained from a 55 year old male Сaucasian familial Alzheimer's disease (AD) patient carrying heterozygous V717I mutation in the APP gene.