scholarly journals Prominent Striatum Amyloid Retention in Early-Onset Familial Alzheimer's Disease With PSEN1 Mutations: A Pilot PET/MR Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Qi Qin ◽  
Liping Fu ◽  
Ruimin Wang ◽  
Jihui Lyu ◽  
Huixuan Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Standardized Uptake Value ◽  
Amyloid Deposition ◽  
Amyloid Pet ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease ◽  
Positive Correlations

Background: With the advancements of amyloid imaging in recent years, this new imaging diagnostic method has aroused great interest from researchers. Till now, little is known regarding amyloid deposition specialty in patients with early-onset familial Alzheimer's disease (EOFAD), and even less is known about its role in cognitive impairments.Objectives: Our study aimed to evaluate the amyloid deposition in five patients with EOFAD, 15 patients with late-onset sporadic AD, and 12 healthy subjects utilizing 11C-labeled Pittsburgh compound-B (11C-PiB) amyloid PET imaging. Moreover, we figured out the correlation between striatal and cortical standardized uptake value ratios (SUVRs). We also investigated the correlation between 11C-PiB retention and cognitive presentation.Results: All patients with EOFAD showed high amyloid deposition in the striatum, a pattern that is not usually seen in patients with late-onset sporadic AD. The SUVR in the striatum, especially in the amygdala, showed significant correlations with cortex SUVR in EOFAD. However, neither striatal nor cortical 11C-PiB retention was related to cognitive decline.Conclusions: The amyloid distribution in patients with EOFAD differs from late-onset sporadic AD, with higher amyloid deposits in the striatum. Our study also demonstrated positive correlations in 11C-PiB retention between the striatum and other cortical areas. We revealed that the distribution of amyloid in the brain is not random but diffuses following the functional and anatomical connections. However, the degree and pattern of amyloid deposition were not correlated with cognitive deficits.

Interfamilial and Intrafamilial Phenotypic Heterogeneity in Familial Alzheimer's Disease

1997 ◽  
Vol 10 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Robert F. Lopez-Alberola ◽  
Warren W. Barker ◽  
Dylan G. Harwood ◽  
David A. Loewenstein ◽  
Peter H. St. George-Hyslop ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Phenotypic Expression ◽  
Phenotypic Heterogeneity ◽  
Cortical Atrophy ◽  
Imaging Features ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease

The features of Alzheimer's disease (AD) are very heterogenous, and some component of the variability of AD is likely to be related to genetic factors. To investigate this question, we evaluated 19 clinical neuropsychiatric and brain imaging features in 32 familial Alzheimer's disease (FAD) kindred, primarily of late onset. Within families, patients displayed a high degree of phenotypic heterogeneity (PH), which occurred irrespective of gender, ethnicity, or apolipoprotein E genotype. Overall, an equivalent amount of PH was observed in both the between- (37%) and within-family (31%) groups. However, for onset age and rate of decline between families, there was greater PH than within families ( P = .002 and P = .01, respectively). A similar trend was found for severity of cortical atrophy ( P = .05). These observations suggest a weak genetic influence, and possibly strong nongenetic influences, on the degree of phenotypic heterogeneity in late-onset FAD. In early-onset AD kindred, a much smaller degree of phenotypic heterogeneity may be expected within families, because genetic influences in phenotypic expression tend to be more prominent in early-onset cases.

scholarly journals Transcriptome analyses of 7-day-old zebrafish larvae possessing a familial Alzheimer’s disease-like mutation in psen1 indicate effects on oxidative phosphorylation, ECM and MCM functions, and iron homeostasis

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yang Dong ◽  
Morgan Newman ◽  
Stephen M. Pederson ◽  
Karissa Barthelson ◽  
Nhi Hin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Phosphorylation ◽  
Transcriptome Analysis ◽  
Iron Homeostasis ◽  
Late Onset ◽  
Wild Type ◽  
Familial Alzheimer’S Disease ◽  
Zebrafish Larvae ◽  
Familial Alzheimer's Disease

Abstract Background Early-onset familial Alzheimer’s disease (EOfAD) is promoted by dominant mutations, enabling the study of Alzheimer’s disease (AD) pathogenic mechanisms through generation of EOfAD-like mutations in animal models. In a previous study, we generated an EOfAD-like mutation, psen1Q96_K97del, in zebrafish and performed transcriptome analysis comparing entire brains from 6-month-old wild type and heterozygous mutant fish. We identified predicted effects on mitochondrial function and endolysosomal acidification. Here we aimed to determine whether similar effects occur in 7 day post fertilization (dpf) zebrafish larvae that might be exploited in screening of chemical libraries to find ameliorative drugs. Results We generated clutches of wild type and heterozygous psen1Q96_K97del 7 dpf larvae using a paired-mating strategy to reduce extraneous genetic variation before performing a comparative transcriptome analysis. We identified 228 differentially expressed genes and performed various bioinformatics analyses to predict cellular functions. Conclusions Our analyses predicted a significant effect on oxidative phosphorylation, consistent with our earlier observations of predicted effects on ATP synthesis in adult heterozygous psen1Q96_K97del brains. The dysregulation of minichromosome maintenance protein complex (MCM) genes strongly contributed to predicted effects on DNA replication and the cell cycle and may explain earlier observations of genome instability due to PSEN1 mutation. The upregulation of crystallin gene expression may be a response to defective activity of mutant Psen1 protein in endolysosomal acidification. Genes related to extracellular matrix (ECM) were downregulated, consistent with previous studies of EOfAD mutant iPSC neurons and postmortem late onset AD brains. Also, changes in expression of genes controlling iron ion transport were observed without identifiable changes in the prevalence of transcripts containing iron responsive elements (IREs) in their 3′ untranslated regions (UTRs). These changes may, therefore, predispose to the apparent iron dyshomeostasis previously observed in 6-month-old heterozygous psen1Q96_K97del EOfAD-like mutant brains.

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
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