ERP generator anomalies in presymptomatic carriers of the Alzheimer's disease E280A PS-1 mutation.
Although subtle anatomical anomalies long precede the onset of clinical symptoms in Alzheimer's disease, their impact on the reorganization of brain networks underlying cognitive functions has not been fully explored. A unique window into this reorganization is provided by presymptomatic cases of familial Alzheimer's disease (FAD). Here we studied neural circuitry related to semantic processing in presymptomatic FAD cases by estimating the intracranial sources of the N400 event-related potential (ERP). ERPs were obtained during a semantic-matching task from 24 presymptomatic carriers and 25 symptomatic carriers of the E280A presenilin-1 (PS-1) mutation, as well as 27 noncarriers (from the same families). As expected, the symptomatic-carrier group performed worse in the matching task and had lower N400 amplitudes than both asymptomatic groups, which did not differ from each other on these variables. However, N400 topography differed in mutation carrier groups with respect to the noncarriers. Intracranial source analysis evinced that the presymptomatic-carriers presented a decrease of N400 generator strength in right inferior-temporal and medial cingulate areas and increased generator strength in the left hippocampus and parahippocampus compared to the controls. This represents alterations in neural function without translation into behavioral impairments. Compared to controls, the symptomatic-carriers presented a similar anatomical shift in the distribution of N400 generators to that found in presymptomatic-carriers, albeit with a larger reduction in generator strength. The redistribution of N400 generators in presymptomatic-carriers indicates that early focal degeneration associated with the mutation induces neural reorganization, possibly contributing to a functional compensation that enables normal performance in the semantic task.
Bobes
María A
MA
Cognitive Neuroscience Department, Cuban Center for Neuroscience, Havana, Cuba. antonieta@cneuro.edu.cu
García
Yuriem Fernández
YF
Lopera
Francisco
F
Quiroz
Yakeel T
YT
Galán
Lídice
L
Vega
Mayrim
M
Trujillo
Nelson
N
Valdes-Sosa
Mitchell
M
Valdes-Sosa
Pedro
P
D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D004569:Electroencephalography; D005071:Evoked Potentials; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D009483:Neuropsychological Tests; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism*; D012660:Semantics; D055815:Young Adult
C508853:PSEN1 protein, human; D053764:Presenilin-1