A Novel AβPP M722K Mutation Affects Amyloid-β Secretion and Tau Phosphorylation and May Cause Early-Onset Familial Alzheimer’s Disease in Chinese Individuals

2015 ◽  
Vol 47 (1) ◽  
pp. 157-165 ◽  
Author(s):  
Qianqian Wang ◽  
Jianping Jia ◽  
Wei Qin ◽  
Liyong Wu ◽  
Dan Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Amyloid Β ◽  
Tau Phosphorylation ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease

scholarly journals Early-Onset Familial Alzheimer's Disease (EOFAD)

2012 ◽  
Vol 39 (4) ◽  
pp. 436-445 ◽  
Author(s):  
Liyong Wu ◽  
Pedro Rosa-Neto ◽  
Ging-Yuek R. Hsiung ◽  
A. Dessa Sadovnick ◽  
Mario Masellis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family History ◽  
Early Onset ◽  
Age At Onset ◽  
Positive Family History ◽  
Amyloid Β ◽  
Neurological Symptoms ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease

Early-onset familial Alzheimer's disease (EOFAD) is a condition characterized by early onset dementia (age at onset < 65 years) and a positive family history for dementia. To date, 230 mutations in presenilin (PS1, PS2) and amyloid precursor protein (APP) genes have been identified in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a common pathogenic pathway in APP synthesis and proteolysis, which lead to excessive production of amyloid β. Compared with sporadic Alzheimer's disease (AD), EOFAD has some distinctive features including early age at onset, positive familial history, a variety of non-cognitive neurological symptoms and signs, and a more aggressive course. There is marked phenotypic heterogeneity among different mutations of EOFAD. Studies in presymptomatic mutation carriers reveal biomarkers abnormalities. EOFAD diagnosis is based on clinical and family history, neurological symptoms and examination, biomarker features, as well as genotyping in some cases. New therapeutic agents targeting amyloid formation may benefit EOFAD individuals.

Nongenetic Factors as Modifiers of the Age of Onset of Familial Alzheimer's Disease

2003 ◽  
Vol 15 (4) ◽  
pp. 337-349 ◽  
Author(s):  
Silvia Mejía ◽  
Margarita Giraldo ◽  
David Pineda ◽  
Alfredo Ardila ◽  
Francisco Lopera
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Logistic Regression ◽  
Early Onset ◽  
Age Of Onset ◽  
Univariate Analysis ◽  
Personal Factors ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease ◽  
High Level

Objective: The purpose of this research was to identify environmental and personal factors that could be related to the variability in the age of onset of familial Alzheimer's disease (FAD) (36–62 years). Methods: A sample was taken of 49 subjects with FAD and with the mutation E280A in the presenilin-1 gene on chromosome 14; the sample was divided into two subgroups: 27 individuals with age of onset of the disease between 36 and 46 years (early onset) and 22 individuals whose disease began between 47 and 62 years (late onset). Information on environmental and personal factors was collected by means of a questionnaire answered by the patients if their clinical condition allowed it, or by their relatives; such information was organized in a categorical way. Comparisons between the two groups for each categorical variable were done by means of the chi-square test. Noncollinear variables that showed statistical significance were included as independent variables in a logistic regression analysis to predict their association with early onset of the disease. Results: Only 5 of the 140 studied variables were different between the two groups in univariate analysis: education, surgical history, type of stressful event, depression, and affective losses. The logistic regression model was constituted by education, depression, and affective losses. High-level education had approximately 15 times more probability of association with an early onset of the disease; both the history of affective losses and depressive symptoms had 4 times more probability of a similar association. Conclusions: The association of high-level education and early onset of the disease could be related to an earlier detection of symptoms, in turn determined by greater intellectual and environmental demands. The occurrence of depression and affective losses has been considered a prodromic manifestation of the disease. Our findings are evidence of high clinical heterogeneity even in a genetically homogeneous group.

scholarly journals Brain Expression of Presenilins in Sporadic and Early-onset, Familial Alzheimer’s Disease

2000 ◽  
Vol 6 (10) ◽  
pp. 878-891 ◽  
Author(s):  
Paul M. Mathews ◽  
Anne M. Cataldo ◽  
Benjamin H. Kao ◽  
Anna G. Rudnicki ◽  
Xi Qin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Familial Alzheimer’S Disease ◽  
Brain Expression ◽  
Familial Alzheimer's Disease

scholarly journals Heavy Tau Burden with Subtle Amyloid β Accumulation in the Cerebral Cortex and Cerebellum in a Case of Familial Alzheimer’s Disease with APP Osaka Mutation

2020 ◽  
Vol 21 (12) ◽  
pp. 4443
Author(s):  
Hiroyuki Shimada ◽  
Shinobu Minatani ◽  
Jun Takeuchi ◽  
Akitoshi Takeda ◽  
Joji Kawabe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Cortex ◽  
Neuronal Degeneration ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Familial Alzheimer’S Disease ◽  
Pet Tracer ◽  
Familial Alzheimer's Disease ◽  
Parietal Cortices

We previously identified a novel mutation in amyloid precursor protein from a Japanese pedigree of familial Alzheimer’s disease, FAD (Osaka). Our previous positron emission tomography (PET) study revealed that amyloid β (Aβ) accumulation was negligible in two sister cases of this pedigree, indicating a possibility that this mutation induces dementia without forming senile plaques. To further explore the relationship between Aβ, tau and neurodegeneration, we performed tau and Aβ PET imaging in the proband of FAD (Osaka) and in patients with sporadic Alzheimer’s disease (SAD) and healthy controls (HCs). The FAD (Osaka) patient showed higher uptake of tau PET tracer in the frontal, lateral temporal, and parietal cortices, posterior cingulate gyrus and precuneus than the HCs (>2.5 SD) and in the lateral temporal and parietal cortices than the SAD patients (>2 SD). Most noticeably, heavy tau tracer accumulation in the cerebellum was found only in the FAD (Osaka) patient. Scatter plot analysis of the two tracers revealed that FAD (Osaka) exhibits a distinguishing pattern with a heavy tau burden and subtle Aβ accumulation in the cerebral cortex and cerebellum. These observations support our hypothesis that Aβ can induce tau accumulation and neuronal degeneration without forming senile plaques.

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