Cognitive function, ageing, and dementia
Philip N. Murphy in The Routledge International Handbook of Psychobiology, 2018
A well-studied genetic variant includes possession of the apolipoprotein E (APOE) gene, which comes in three forms (APOE ε2; APOE ε3; APOE ε4). Humans have two copies of this gene, which may contain any combination of the alleles ε2–4. The APOE ε4 allele is thought to increase risk of AD three- to four-fold, depending on whether one or two copies are inherited (Verghese, Castellano, & Holtzman, 2011). In contrast, APOE ε2 is thought to be mildly protective (Corder et al., 1994). Some studies also report links between APOE and vascular dementia (VaD), although a consensus for this link is less well established (Verghese et al., 2011). Common genes associated with frontotemporal dementia (FTD) include MAPT (for tau protein), GRN (for the protein progranulin) and C9orf72 (Whitwell et al., 2012). While demographic and genetic factors cannot be explicitly modified, knowledge of high-risk or susceptible individuals can be used to target prevention programmes.
Phytotherapeutic Potential For the Treatment of Alzheimer’s Disease
Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu in Phytomedicine and Alzheimer’s Disease, 2020
Apolipoprotein E is also a causative agent in the development of AD. Different form of apolipoprotein E are present, like apolipoproteins E2, 3, and 4. Glial cells of the brain, which are also called astrocytes, produce these proteins. The risk of developing AD is greater in the presence of higher apolipoprotein E4 concentrations (Aaronson, Van Den Eeden et al. 2017). If the level of this protein increases, then the probability of death is also increased (Harris, Brecht et al. 2003). AD is also associated with E693G mutations in a gene encoding an amyloid precursor protein (Nilsberth, Westlind-Danielsson et al. 2001). Furthermore, AD is caused by oxidative stress because, in this situation, demand by the brain for oxygen is increased (Butterfield and Lauderback 2002). AD is also associated with some pathogens like Chlamydia pneumoniae, which enter the brain tissue and damage brain cells (Harris, Brecht et al. 2003). AD is more common in females, smokers, obese people, patients with high blood pressure or a high level of cholesterol, whereas previous trauma, changes in sleep pattern, and Down syndrome can all increase the risk of AD (Simonson 2018).
Dementia in Parkinson's disease
John O'Brien, Ian McKeith, David Ames, Edmond Chiu in Dementia with Lewy Bodies and Parkinson's Disease Dementia, 2005
Although PD was long thought not to be a genetic disorder, over the past few years, several genes for the disorder have been cloned, including a-synuclein and parkin, both of which are involved in the ubiquitin- dependent protein degradation pathway (Gwinn-Hardy, 2002). The relationship of these genes to dementia is not clear, but there are mutation carriers both with PD and with PDD (Muenter et al, 1998). Several studies have explored the effect of apolipoprotein E (ApoE) polymorphism, a risk factor for AD, on the risk for PD and dementia, with conflicting results. Increased risk of PD and, in particular, PDD, in carriers of the ApoE s2 allele has been reported (Harhangi et al, 2000), while another study reported an association between the ApoE r,4 allele and Alzheimer pathology in PD patients
Prevalence of candidate single nucleotide polymorphisms on p53, IL-11, IL-10, VEGF and APOE in patients with repeated implantation failure (RIF) and pregnancy loss (RPL)
Published in Human Fertility, 2020
Azahara Turienzo, Belén Lledó, José A. Ortiz, Ruth Morales, Juan Sanz, Joaquín Llácer, Rafael Bernabeu
Finally, other proteins that are not major players might also affect the correct implantation and development of the pregnancy. For example, apolipoprotein E (APOE) is involved in the transport of lipoproteins, lipid soluble vitamins and cholesterol into the lymphatic system and subsequently into the bloodstream (Mahley, Weisgraber, & Huang, 2009). A deficient protein could produce lipid accumulation in the bloodstream increasing thrombotic risk. The ApoE (19q13) gene consists of four exons. It has three polymorphic isoforms: ApoE E2 (cys 112, cys 158), ApoE E3 (cys 112, arg 158) and ApoE E4 (arg 112, arg 158) that produce six different genotypes: E2/E2, E2/E3, E2/E4, E3/E3, E3/E4 and E4/E4. Different genotypes have been associated with reproductive problems mainly RPL (Li, Chen, Wu, & Li, 2014).
Factors influencing recovery from mild traumatic brain injury
Published in Brain Injury, 2020
Leslie Weaver Johnson, Kristine Lundgren, Vincent Henrich, Susan Phillips
Recently, researchers have begun to examine the potential role of genetics in determining functional outcome after TBI. Specifically, investigators have studied the role of apolipoprotein E (APOE) on cognitive recovery and long-term functional outcome (19). The APOE gene provides instructions for making a protein called apolipoprotein E (apoE). This protein combines with fats in the body to form molecules called lipoproteins which the brain uses to maintain, restore, and/or stabilize its synaptic connections, otherwise known as plasticity (20). This plasticity is likely a key contributor in the rehabilitation process after brain injury. In its normal functioning, apoE does not cross the blood-brain barrier. However, in response to injury, the apoE protein may positively influence the central nervous system by acting as an anti-excitotoxic, antioxidant, and/or anti-inflammatory agent (14).
Anti-amyloid-β protein agents for the treatment of Alzheimer’s disease: an update on emerging drugs
Published in Expert Opinion on Emerging Drugs, 2020
Madia Lozupone, Vincenzo Solfrizzi, Francesca D’Urso, Ilaria Di Gioia, Rodolfo Sardone, Vittorio Dibello, Roberta Stallone, Angelo Liguori, Chiara Ciritella, Antonio Daniele, Antonello Bellomo, Davide Seripa, Francesco Panza
Alzheimer disease (AD), a multifactorial, heterogeneous, and progressive neurodegenerative disease with a long presymptomatic phase, is clinically characterized by cognitive, behavioral, and functional impairment with loss of independence. In the USA, an estimated 5.8 million people of all ages are living with AD in 2019 [1]. AD was the sixth most common cause of death in 2019 and by 2050, the number of people age 65 and older with AD may grow to a projected 13.8 million, barring the development of medical breakthroughs to prevent, slow, or cure AD [1]. In the last three decades, notwithstanding the great efforts spent in the search of a disease-modifying treatment for AD, current therapies are only symptomatic and do not affect disease progression [2]. The brain pathology of senile plaques (SP) has become the gold standard for diagnosing AD, although they seem not to be directly correlated with severity of deficits in patients with AD. The amyloid cascade hypothesis states that brain amyloid-β (Aβ) peptide deposition drives tau phosphorylation, tangle formation, synaptic loss, neuronal death, and cognitive impairment [2]. Aβ accumulation has also been linked to the apolipoprotein E (APOE) ε4 allele, the most important genetic risk factor associated with sporadic AD.
Related Knowledge Centers
- Alzheimer's Disease
- Cardiovascular Disease
- Gene
- Apolipoprotein
- Chylomicron
- Very Low-Density Lipoprotein
- Intermediate-Density Lipoprotein
- High-Density Lipoprotein
- Ldl Receptor
- Catabolism