The cystatin C gene as a novel genetic risk factor for late onset Alzheimer's disease

2000 ◽  
Vol 21 ◽  
pp. 204 ◽  
Author(s):  
Fiona Crawford ◽  
Melissa J. Freeman ◽  
John Schinka ◽  
Laila Abdullah ◽  
Mike Gold ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Cystatin C ◽  
Genetic Risk ◽  
Late Onset ◽  
Genetic Risk Factor

scholarly journals ApoE4 attenuates cortical neuronal activity and impairs memory in young apoE4 rats

2021 ◽  
Author(s):  
Ilona Har-Paz ◽  
Elor Arieli ◽  
Anan Moran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Neuronal Activity ◽  
Genetic Risk ◽  
Cortical Neurons ◽  
Late Onset ◽  
Genetic Risk Factor ◽  
Normal Brain ◽  
Brain Functions

AbstractThe E4 allele of apolipoprotein E (apoE4) is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). However, apoE4 may cause innate brain abnormalities before the appearance of AD related neuropathology. Understanding these primary dysfunctions is vital for early detection of AD and the development of therapeutic strategies for it. Recently we have shown impaired extra-hippocampal memory in young apoE4 mice – a deficit that was correlated with attenuated structural pre-synaptic plasticity in cortical and subcortical regions. Here we test the hypothesis that these early structural deficits impact learning via changes in basal and stimuli evoked neuronal activity. We recorded extracellular neuronal activity from the gustatory cortex (GC) of three-month-old humanized apoE4 and wildtype rats, before and after conditioned taste aversion (CTA) training. Despite normal sucrose drinking behavior before CTA, young apoE4 rats showed impaired CTA learning, consistent with our previous results in apoE4 mice. This behavioral deficit was correlated with decreased basal and taste-evoked firing rates in both putative excitatory and inhibitory GC neurons. Single neuron and ensemble analyses of taste coding demonstrated that apoE4 neurons could be used to correctly classify tastes, but were unable to undergo plasticity to support learning. Our results suggest that apoE4 impacts brain excitability and plasticity early in life and may act as an initiator for later AD pathologies.Significant statementThe ApoE4 allele is the strongest genetic risk-factor for late-onset Alzheimer’s disease (AD), yet the link between apoE4 and AD is still unclear. Recent molecular and in-vitro studies suggest that apoE4 interferes with normal brain functions decades before the development of its related AD neuropathology. Here we recorded the activity of cortical neurons from young apoE4 rats during extra-hippocampal learning to study early apoE4 neuronal activity abnormalities, and their effects over coding capacities. We show that apoE4 drastically reduces basal and stimuli-evoked cortical activity in both excitatory and inhibitory neurons. The apoE4-induced activity attenuation did not prevent coding of stimuli identity and valence, but impaired capacity to undergo activity changes to support learning. Our findings support the hypothesis that apoE4 interfere with normal neuronal plasticity early in life; a deficit that may lead to late-onset AD development.

scholarly journals Association between the APOE ε4 Allele and Late-Onset Alzheimer’s Disease in an Ecuadorian Mestizo Population

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Stefany Montufar ◽  
Cristian Calero ◽  
Rodrigo Vinueza ◽  
Patricio Correa ◽  
Andrea Carrera-Gonzalez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Genetic Risk ◽  
Disease Risk ◽  
Late Onset ◽  
Genetic Risk Factor ◽  
Genotype Frequencies ◽  
Healthy Control ◽  
Genetic Contributions

Alzheimer’s disease (AD) is the most common neurodegenerative disease. It has two main pathological hallmarks: amyloid plaques and neurofibrillary tangles. The APOE ε4 allele has been recognized as the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD) in several populations worldwide, yet the risk varies by region and ethnicity. The aims of this study were to describe APOE allele and genotype frequencies and examine the relationship between the APOE ε4 allele and LOAD risk in an Ecuadorian Mestizo population. We carried out a case-control study comprising 56 individuals clinically diagnosed with probable AD (≥65 years of age) and 58 unrelated healthy control subjects (≥65 years of age). Genotyping was performed using the real-time PCR method. Our data showed that allelic and genotypic frequencies follow the trends observed in most worldwide populations. We also found a high-risk association between APOE ε4 allele carriers and LOAD (OR = 7.286; 95% CI = 2.824–18.799; p<0.001). Therefore, we concluded that APOE ε4 must be considered an important genetic risk factor for LOAD in the Ecuadorian Mestizo population. Additionally, we suggest that in mixed populations the effects of admixture and ethnic identity should be differentiated when evaluating genetic contributions to Alzheimer’s disease risk.

scholarly journals Molecular Insight into the Therapeutic Promise of Targeting APOE4 for Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Abdullah Al Mamun ◽  
Md. Sahab Uddin ◽  
Md. Fahim Bin Bashar ◽  
Sonia Zaman ◽  
Yesmin Begum ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Genetic Risk ◽  
Late Onset ◽  
Neurofibrillary Tangle ◽  
Cerebrovascular Diseases ◽  
Genetic Risk Factor ◽  
Synaptic Loss ◽  
Novel Drugs

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that causes chronic cognitive dysfunction. Most of the AD cases are late onset, and the apolipoprotein E (APOE) isoform is a key genetic risk factor. The APOE gene has 3 key alleles in humans including APOE2, APOE3, and APOE4. Among them, APOE4 is the most potent genetic risk factor for late-onset AD (LOAD), while APOE2 has a defensive effect. Research data suggest that APOE4 leads to the pathogenesis of AD through various processes such as accelerated beta-amyloid aggregations that raised neurofibrillary tangle formation, cerebrovascular diseases, aggravated neuroinflammation, and synaptic loss. However, the precise mode of actions regarding in what way APOE4 leads to AD pathology remains unclear. Since APOE contributes to several pathological pathways of AD, targeting APOE4 might serve as a promising strategy for the development of novel drugs to combat AD. In this review, we focus on the recent studies about APOE4-targeted therapeutic strategies that have been advanced in animal models and are being prepared for use in humans for the management of AD.

ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease

2005 ◽  
Vol 18 (1) ◽  
pp. 119-125 ◽  
Author(s):  
Sandrine Macé ◽  
Emmanuelle Cousin ◽  
Sylvain Ricard ◽  
Emmanuelle Génin ◽  
Emmanuel Spanakis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Genetic Risk ◽  
Early Onset ◽  
Genetic Risk Factor ◽  
Early Onset Alzheimer’S Disease

A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer's disease

Neurology ◽  
2000 ◽  
Vol 55 (6) ◽  
pp. 763-768 ◽  
Author(s):  
F. C. Crawford ◽  
M. J. Freeman ◽  
J. A. Schinka ◽  
L. I. Abdullah ◽  
M. Gold ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Cystatin C ◽  
Late Onset

Is HCRTR2 a Genetic Risk Factor for Alzheimer's Disease?

2014 ◽  
Vol 38 (3-4) ◽  
pp. 245-253 ◽  
Author(s):  
Salvatore Gallone ◽  
Silvia Boschi ◽  
Elisa Rubino ◽  
Paola De Martino ◽  
Elio Scarpini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Genetic Risk ◽  
Genetic Risk Factor
Sign in / Sign up

Export Citation Format

Share Document