An unexpected discovery of a novel potentially pathogenic APP gene variant: a case report of slowly progressive Alzheimer's disease with prominent cerebral amyloid angiopathy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064190%3A_____%2F26%3A10001460" target="_blank" >RIV/00064190:_____/26:10001460 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.3389/fnins.2025.1703718" target="_blank" >https://doi.org/10.3389/fnins.2025.1703718</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fnins.2025.1703718" target="_blank" >10.3389/fnins.2025.1703718</a>

Jazyk výsledku

angličtina

Název v původním jazyce

An unexpected discovery of a novel potentially pathogenic APP gene variant: a case report of slowly progressive Alzheimer's disease with prominent cerebral amyloid angiopathy

Popis výsledku v původním jazyce

Amyloid precursor protein (APP) plays an essential role in brain function and development. Variants in the APP gene are associated with both familial Alzheimer&apos;s disease and cerebral amyloid angiopathy. We report a case of early onset, slowly progressive mixed dementia with a newly identified APP variant. The patient developed mild cognitive impairment at age 51, followed by neuropsychiatric symptoms, seizures, and progressive white matter changes. Despite a fluctuating clinical course, significant deterioration occurred later, culminating in death at age 77. Genetic testing revealed an APP c.2086G &gt; A (p.Gly696Ser) variant, currently classified as a variant of uncertain significance (VUS). Postmortem examination showed definite AD neuropathologic changes, with fully blown amyloid pathology including amyloid deposits in plaques as well as in severe generalized cerebral angiopathy with concomitant advanced FTLD-tau pathology. In silico analysis of the variant&apos;s impact was performed, and the inconclusive results are discussed later.

Název v anglickém jazyce

An unexpected discovery of a novel potentially pathogenic APP gene variant: a case report of slowly progressive Alzheimer's disease with prominent cerebral amyloid angiopathy

Popis výsledku anglicky

Amyloid precursor protein (APP) plays an essential role in brain function and development. Variants in the APP gene are associated with both familial Alzheimer&apos;s disease and cerebral amyloid angiopathy. We report a case of early onset, slowly progressive mixed dementia with a newly identified APP variant. The patient developed mild cognitive impairment at age 51, followed by neuropsychiatric symptoms, seizures, and progressive white matter changes. Despite a fluctuating clinical course, significant deterioration occurred later, culminating in death at age 77. Genetic testing revealed an APP c.2086G &gt; A (p.Gly696Ser) variant, currently classified as a variant of uncertain significance (VUS). Postmortem examination showed definite AD neuropathologic changes, with fully blown amyloid pathology including amyloid deposits in plaques as well as in severe generalized cerebral angiopathy with concomitant advanced FTLD-tau pathology. In silico analysis of the variant&apos;s impact was performed, and the inconclusive results are discussed later.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/NU23-04-00173" target="_blank" >NU23-04-00173: Využití metody RT-QuIC pro zpřesnění diagnostiky neurodegenerativních onemocnění: Prospektivní a retrospektivní studie</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2026

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

FRONTIERS IN NEUROSCIENCE

ISSN

—

e-ISSN

1662-453X

Svazek periodika

19

Číslo periodika v rámci svazku

neuveden

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

8

Strana od-do

nestránkováno

Kód UT WoS článku

001663212300001

EID výsledku v databázi Scopus

2-s2.0-105027673948