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

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

2014 ◽  
Vol 5 (1) ◽  
pp. 38-42 ◽  
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.

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.

P4-079 Is variation in the gene encoding insulin-degrading enzyme (IDE) a risk factor in late-onset Alzheimer's disease?

2004 ◽  
Vol 25 ◽  
pp. S496-S497
Author(s):  
Petra Nowotny ◽  
Scott Smemo ◽  
Tony Hinrichs ◽  
Peter Holmans ◽  
Kristina Tracey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Late Onset ◽  
Insulin Degrading Enzyme ◽  
Gene Encoding ◽  
Degrading Enzyme

APOE -491 promoter polymorphism is a risk factor for late-onset Alzheimer's disease

Neurology ◽  
1999 ◽  
Vol 53 (8) ◽  
pp. 1888-1888 ◽  
Author(s):  
V. M. Casadei ◽  
C. Ferri ◽  
F. Veglia ◽  
A. Gavazzi ◽  
G. Salani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Late Onset ◽  
Promoter Polymorphism

scholarly journals Evidence for Sub-Haplogroup H5 of Mitochondrial DNA as a Risk Factor for Late Onset Alzheimer's Disease

PLoS ONE ◽  
2010 ◽  
Vol 5 (8) ◽  
pp. e12037 ◽  
Author(s):  
Aurelia Santoro ◽  
Valentina Balbi ◽  
Elisa Balducci ◽  
Chiara Pirazzini ◽  
Francesca Rosini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dna ◽  
Risk Factor ◽  
Late Onset

scholarly journals The Alzheimer’s disease risk factor APOE4 drives pro-inflammation in human astrocytes via HDAC-dependent repression of TAGLN3

2021 ◽  
Author(s):  
Laurie Arnaud ◽  
Philippe Benech ◽  
Louise Greetham ◽  
Delphine Stephan ◽  
Angélique Jimenez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Transcriptional Repression ◽  
Inflammatory Responses ◽  
Disease Risk ◽  
Late Onset ◽  
Patient Specific ◽  
Potential Biomarker ◽  
Induced Pluripotent

ABSTRACTThe Apolipoprotein E4 (APOE4) is the major allelic risk factor for late-onset Alzheimer’s disease (AD). APOE4 associates with a pro-inflammatory phenotype increasingly considered as critical in AD initiation and progression. Yet, the mechanisms driving an APOE4-dependent neuroinflammation remain unelucidated. Leveraging patient specific human induced Pluripotent Stem Cells (iPSCs) we demonstrate inflammatory chronicity and hyperactivated responses upon cytokines in human APOE4 astrocytes via a novel mechanism. We uncovered that APOE4 represses Transgelin 3 (TAGLN3), a new interacting partner of IκBα, thus increasing the NF-kB activity. The transcriptional repression of TAGLN3 was shown to result from an APOE4-dependent histone deacetylase (HDAC) activity. The functional relevance of TAGLN3 was demonstrated by the attenuation of APOE4-driven neuroinflammation after TAGLN3 supplementation. Importantly, TAGLN3 downregulation was confirmed in the brain of AD patients. Our findings highlight the APOE4-TAGLN3 axis as a new pathogenic pathway that paves the way for the development of therapeutics to prevent maladaptive inflammatory responses in APOE4 carriers, while placing TAGLN3 downregulation as a potential biomarker of AD.GRAPHICAL ABSTRACT

scholarly journals The Molecular Basis for Apolipoprotein E4 as the Major Risk Factor for Late-Onset Alzheimer's Disease

2019 ◽  
Vol 431 (12) ◽  
pp. 2248-2265 ◽  
Author(s):  
Ana-Caroline Raulin ◽  
Lucas Kraft ◽  
Youssra K. Al-Hilaly ◽  
Wei-Feng Xue ◽  
John E. McGeehan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Molecular Basis ◽  
Late Onset ◽  
Major Risk Factor ◽  
Apolipoprotein E4

Confirmation of the  4 allele of the apolipoprotein E gene as a risk factor for late-onset Alzheimer's disease

Neurology ◽  
1994 ◽  
Vol 44 (2) ◽  
pp. 342-342 ◽  
Author(s):  
T. Brousseau ◽  
S. Legrain ◽  
C. Berr ◽  
V. Gourlet ◽  
O. Vidal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Apolipoprotein E ◽  
Late Onset ◽  
E Gene ◽  
Apolipoprotein E Gene
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