Alzheimer's disease onset time linked to HLA-2A

The Lancet ◽  
1997 ◽  
Vol 350 (9077) ◽  
pp. 568
Author(s):  
Michael McCarthy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Onset ◽  
Onset Time

scholarly journals Brain mechanisms underlying neuropsychiatric symptoms in Alzheimer’s disease: a systematic review of symptom-general and –specific lesion patterns

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yaojing Chen ◽  
Mingxi Dang ◽  
Zhanjun Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Neuropsychiatric Symptoms ◽  
Onset Time ◽  
Anterior Cingulate ◽  
Neural Basis ◽  
Preclinical Ad ◽  
Disease Stages ◽  
Mild Cognitive Impairment Stage

AbstractNeuropsychiatric symptoms (NPSs) are common in patients with Alzheimer’s disease (AD) and are associated with accelerated cognitive impairment and earlier deaths. This review aims to explore the neural pathogenesis of NPSs in AD and its association with the progression of AD. We first provide a literature overview on the onset times of NPSs. Different NPSs occur in different disease stages of AD, but most symptoms appear in the preclinical AD or mild cognitive impairment stage and develop progressively. Next, we describe symptom-general and -specific patterns of brain lesions. Generally, the anterior cingulate cortex is a commonly damaged region across all symptoms, and the prefrontal cortex, especially the orbitofrontal cortex, is also a critical region associated with most NPSs. In contrast, the anterior cingulate-subcortical circuit is specifically related to apathy in AD, the frontal-limbic circuit is related to depression, and the amygdala circuit is related to anxiety. Finally, we elucidate the associations between the NPSs and AD by combining the onset time with the neural basis of NPSs.

scholarly journals Conditional Deletion of Prnp Rescues Behavioral and Synaptic Deficits after Disease Onset in Transgenic Alzheimer's Disease

2017 ◽  
Vol 37 (38) ◽  
pp. 9207-9221 ◽  
Author(s):  
Santiago V. Salazar ◽  
Christopher Gallardo ◽  
Adam C. Kaufman ◽  
Charlotte S. Herber ◽  
Laura T. Haas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Onset ◽  
Conditional Deletion

scholarly journals Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study

Brain ◽  
2020 ◽  
Author(s):  
Longfei Jia ◽  
Fangyu Li ◽  
Cuibai Wei ◽  
Min Zhu ◽  
Qiumin Qu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Study ◽  
Predictive Models ◽  
Genome Wide Association Study ◽  
Disease Onset ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Risk Variants ◽  
Genome Wide

Abstract Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer’s disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer’s disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer’s disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10−19, 2.49 × 10−23, 1.35 × 10−67, and 4.81 × 10−9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P < 5.0 × 10−8). Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis. Based on their possible roles in the development of Alzheimer’s disease, we used different combinations of these variants and the apolipoprotein E status and successively built 11 predictive models. The predictive models include relatively few single nucleotide polymorphisms useful for clinical practice, in which the maximum number was 13 and the minimum was only four. These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages. Finally, these models were validated using a separate longitudinal cohort of 5474 individuals. The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer’s disease, suggesting that our models can predict Alzheimer’s disease onset in a population with genetic susceptibility. The effectiveness of the models for predicting Alzheimer’s disease onset confirmed the contributions of these identified variants to disease pathogenesis. In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer’s disease onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants, and particularly for young individuals seeking genetic consultation.

P1-235: TOMM40 “523” Genotype Affects Age of Alzheimer's Disease Onset Differentially by Race

2011 ◽  
Vol 7 ◽  
pp. S186-S186
Author(s):  
Kathleen Hayden ◽  
Michael Lutz ◽  
Ann Saunders ◽  
Heather Romero ◽  
James Burke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Onset

scholarly journals Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis

2018 ◽  
Vol 115 (8) ◽  
pp. 1697-1706 ◽  
Author(s):  
Xiaopu Zhou ◽  
Yu Chen ◽  
Kin Y. Mok ◽  
Qianhua Zhao ◽  
Keliang Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Chinese Population ◽  
Disease Onset ◽  
The Elderly ◽  
Common Variants ◽  
Altered Expression ◽  
Risk Variants ◽  
Regulatory Effects

Alzheimer’s disease (AD) is a leading cause of mortality among the elderly. We performed a whole-genome sequencing study of AD in the Chinese population. In addition to the variants identified in or around the APOE locus (sentinel variant rs73052335, P = 1.44 × 10−14), two common variants, GCH1 (rs72713460, P = 4.36 × 10−5) and KCNJ15 (rs928771, P = 3.60 × 10−6), were identified and further verified for their possible risk effects for AD in three small non-Asian AD cohorts. Genotype–phenotype analysis showed that KCNJ15 variant rs928771 affects the onset age of AD, with earlier disease onset in minor allele carriers. In addition, altered expression level of the KCNJ15 transcript can be observed in the blood of AD subjects. Moreover, the risk variants of GCH1 and KCNJ15 are associated with changes in their transcript levels in specific tissues, as well as changes of plasma biomarkers levels in AD subjects. Importantly, network analysis of hippocampus and blood transcriptome datasets suggests that the risk variants in the APOE, GCH1, and KCNJ15 loci might exert their functions through their regulatory effects on immune-related pathways. Taking these data together, we identified common variants of GCH1 and KCNJ15 in the Chinese population that contribute to AD risk. These variants may exert their functional effects through the immune system.

scholarly journals Bridging the Gap between Alzheimer’s Disease and Alzheimer’s-like Diseases in Animals

2019 ◽  
Vol 20 (7) ◽  
pp. 1664 ◽  
Author(s):  
Anita Gołaszewska ◽  
Wojciech Bik ◽  
Tomasz Motyl ◽  
Arkadiusz Orzechowski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Hot Spot ◽  
Senile Plaques ◽  
Disease Onset ◽  
Suitable Model ◽  
In Vivo Models ◽  
Average Life Span

The average life span steadily grows in humans and in animals kept as pets or left in sanctuaries making the issue of elderly-associated cognitive impairment a hot-spot for scientists. Alzheimer’s disease (AD) is the most prevalent cause of progressive mental deterioration in aging humans, and there is a growing body of evidence that similar disorders (Alzheimer’s-like diseases, ALD) are observed in animals, more than ever found in senescent individuals. This review reveals up to date knowledge in pathogenesis, hallmarks, diagnostic approaches and modalities in AD faced up with ALD related to different animal species. If found at necropsy, there are striking similarities between senile plaques (SP) and neurofibrillary tangles (NFT) in human and animal brains. Also, the set of clinical symptoms in ALD resembles that observed in AD. At molecular and microscopic levels, the human and animal brain histopathology in AD and ALD shows a great resemblance. AD is fatal, and the etiology is still unknown, although the myriad of efforts and techniques were employed in order to decipher the molecular mechanisms of disease onset and its progression. Nowadays, according to an increasing number of cases reported in animals, apparently, biochemistry of AD and ALD has a lot in common. Described observations point to the importance of extensive in vivo models and extensive pre-clinical studies on aging animals as a suitable model for AD disease.

scholarly journals Association of cancer history with Alzheimer's disease onset and structural brain changes

2014 ◽  
Vol 5 ◽  
Author(s):  
Kelly N. H. Nudelman ◽  
Shannon L. Risacher ◽  
John D. West ◽  
Brenna C. McDonald ◽  
Sujuan Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Onset ◽  
Cancer History ◽  
Brain Changes ◽  
Structural Brain
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