Naslov
Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation (Neurosci. Lett. 487 (2011) 287–292)

Autori
Ringman, John M. ; Gylys, Karen H. ; Medina, Luis D. ; Fox, Michelle ; Kepe, Vladimir ; Flores, Deborah L. ; Apostolova, Liana G. ; Barrio, Jorge R. ; Small, Gary ; Silverman, Daniel H. ; Siu, Erin ; Cederbaum, Stephen ; Hećimović, Silva ; Malnar, Martina ; Chakravertyg, Suma ; Goate, Alison M. ; Bird, Thomas D. ; Leverenz, James B.

Izvornik
Neuroscience letters (0304-3940) 491 (2011), 2; 163-163

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, ispravak, znanstveni

Ključne riječi
Alzheimer’s disease; PSEN1; S212Y; amyloid imaging; FDDNP; cerebrospinal fluid; neuropathology; FDG; Positron emission tomography; tau; beta-amyloid; striatum

Sažetak
Familial Alzheimer’s disease (AD) due to PSEN1 mutations provides a unique opportunity to study the behavior of AD biomarkers in persons in whom the diagnosis is certain. Here we describe a 55 year-old woman with clinically probable AD and a novel PSEN1 mutation who underwent genetic, clinical, biochemical and imaging assessments, including nuclear imaging with FDDNP. Neuropsychological testing confirmed deficits in memory with more minor deficits in visuospatial and language function. CSF t-tau and p-tau181 were markedly elevated and Abeta42 levels reduced. FDG-PET revealed hypometabolism in the left parietotemporal cortex. FDDNP-PET showed increased global binding of tracer in medial temporal and parietal lobes and in the head of the caudate and anterior putamen bilaterally. Her similarly affected brother died and the diagnosis of AD was confirmed neuropathologically. The striatum demonstrated amyloid pathology and marked neurofibrillary pathology beyond that typically seen in late-onset AD. A novel S212Y substitution in PSEN1 was present in the index patient and in her affected brother but not in an older unaffected sister. An in-vitro assay in which the S212Y mutation was introduced in cell culture confirmed that it was associated with increased production of Abeta42.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA