Genetic Variants Related to Lipid Metabolism as a Risk Factor for Late Onset Alzheimer's Disease in Brazilian Population (P05.077)

Background: Genetic polymorphisms in genes regulating cholesterol metabolism have been suggested to risk factor of developing Alzheimer’s disease (AD). Objective: to analyze the frequency of polymorphisms apolipoprotein E (APOE-HhaI) and adenosine triphosphate binding cassette transporter 1 (ABCA1-StyI) in patients with late-onset AD. Design: case-control study. Participants: We studied 166 subjects (≥65 years old): Study Group (SG)- 88 patients and Control Group (CG)- 88 without dementia. Setting: The polymorphisms were determined using the polymorphism chain reaction and restriction fragment length polymorphism (PCR-RFLP) methods. It was applied Fisher's exact/chi-square tests (P<0.05). Results: Genotypes with APOE*4 prevailed in SG. The genotypic combination between APOE-HhaI and ABCA1-StyI polymorphisms showed a prevalence of heterozygous genotypes of risk for AD. Conclusion: Although genetic variants for ABCA1-StyI alone does not differentiate patients and controls, the G allele in synergy with APOE*4 allele is highlighted in patients suggesting the influence of ABCA1 in the disease.

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Emerging evidence for associations between periodontitis and the development of Alzheimer’s disease

Faculty Dental Journal ◽

10.1308/204268514x13859766312719 ◽

2014 ◽

Vol 5 (1) ◽

pp. 38-42 ◽

Cited By ~ 5

Author(s):

Sophie Poole ◽

Sim K Singhrao ◽

St John Crean

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Immune Responses ◽

Periodontal Disease ◽

Potential Risk ◽

Inflammatory Disease ◽

Pathogenic Bacteria ◽

Late Onset ◽

Systemic Circulation

Periodontal disease (PD) is an inflammatory disease affecting tooth-supporting tissues in which interaction of specific bacteria and the host’s immune responses play a pivotal role. The pathogenic bacteria associated with PD are a source of systemic inflammation as they have the ability to enter systemic circulation during everyday tasks such as brushing teeth and chewing food. Alzheimer’s disease (AD) is a form of dementia whereby inflammation is thought to play a key role in its pathogenesis and the risk of developing the disease increasing with age. The exact aetiology of the late-onset AD is unknown but peripheral infections are being considered as a potential risk factor.

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

10.1101/2021.01.14.426651 ◽

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.

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P1-155: ASSOCIATION BETWEEN COMMON GENETIC VARIANTS OF LATE-ONSET ALZHEIMER'S DISEASE AND FAMILY HISTORY OF ALZHEIMER'S DEMENTIA: A PRELIMINARY STUDY

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.159 ◽

2006 ◽

Vol 14 (7S_Part_6) ◽

pp. P336-P336

Author(s):

Min Soo Byun ◽

Jieun Seo ◽

Dahyun Yi ◽

Jun Ho Lee ◽

Younghwa Lee ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Family History ◽

Genetic Variants ◽

Late Onset ◽

Alzheimer’S Dementia ◽

Alzheimer's Dementia ◽

Common Genetic Variants ◽

History Of ◽

Preliminary Study

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Association Study of Genetic Variants inCDKN2A/CDKN2BGenes/Loci with Late-Onset Alzheimer's Disease

International Journal of Alzheimer s Disease ◽

10.4061/2011/374631 ◽

2011 ◽

Vol 2011 ◽

pp. 1-4

Author(s):

Andrea Tedde ◽

Irene Piaceri ◽

Silvia Bagnoli ◽

Ersilia Lucenteforte ◽

Uwe Ueberham ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Genetic Variants ◽

Genetic Variant ◽

Case Control Study ◽

Late Onset ◽

Common Genetic Variant ◽

Genome Wide ◽

Control Study

Alzheimer's disease (AD) is the most common form of dementia clinically characterized by progressive impairment of memory and other cognitive functions. Many genetic researches in AD identified one common genetic variant (ε4) in Apolipoprotein E (APOE) gene as a risk factor for the disease. Two independent genome-wide studies demonstrated a new locus on chromosome 9p21.3 implicated in Late-Onset Alzheimer's Disease (LOAD) susceptibility in Caucasians. In the present study, we investigated the role of three SNP's in theCDKN2Agene (rs15515, rs3731246, and rs3731211) and one in theCDKN2Bgene (rs598664) located in 9p21.3 using an association case-control study carried out in a group of Caucasian subjects including 238 LOAD cases and 250 controls. The role ofCDKN2AandCDKN2Bgenetic variants in AD is not confirmed in our LOAD patients, and further studies are needed to elucidate the role of these genes in the susceptibility of AD.

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