Apolipoprotein E ?4 is associated with hippocampal volume reduction in females with alcoholism

Abstract

There is evidence that a higher incidence of diverse neurodegenerative diseases is associated with the apolipoprotein E epsilon4 allele (ApoE4). Most recently it has been found that the ApoE4 allele is specifically related to an accelerated hippocampal atrophy in patients with Alzheimer's disease. Therefore, the aim of the present study was to investigate the association between ApoE4 genotypes and brain hippocampal volume reduction in alcoholics by using volumetric high-resolution MR imaging. In the present study, female alcoholics with the ApoE4 genotype were found to have significantly smaller hippocampal volumes than those not carrying an epsilon4 allele (ANOVA, p < 0.05), whereas no differences in hippocampal volume were seen in male alcoholics. Since hippocampal volume reduction is lately discussed to be proportional to brain atrophy, we propose that the alcohol-related brain atrophy in patients suffering from chronic alcoholism, is more pronounced in female carriers of the apoE epsilon4 allele. These findings indicate a genetic disposition for alcohol related brain atrophy in female carrying the ApoE4 genotype, which may also explain why female alcoholics are more susceptible to alcohol-induced brain damage.

The apolipoprotein E epsilon 4 allele is associated with ventricular expansion rate and surface morphology in dementia and normal aging

“…ApoE participates in general cellular pathways designed to respond adaptively to many environmental, metabolic, and genetic stimuli (Mahley and Huang, 2012b). Our findings, combined with earlier investigations showing that ApoE-ε4 is a risk factor for other neurological conditions (Ely et al, 2007), is associated with reduced capacity for neuronal regeneration (Friedman et al, 1999) and modulates the neurotoxic effects of alcohol abuse (Bleich et al, 2003; Wilhelm et al, 2008), suggest that the selective enrollment of ApoE-ε4 carriers (or post-hoc stratification by ApoE status) may empower clinical trials of other disorders, such as alcoholism and traumatic brain injury.…”

“…ApoE-ε4 also predicts poor neurological outcome after traumatic brain injury (Friedman et al, 1999) and cerebral hemorrhage (Alberts et al, 1995). Moreover, the same allele is a risk factor for hippocampal volume loss in alcoholics (Bleich et al, 2003; Wilhelm et al, 2008), suggesting that ApoE-ε4 may also promote neurodegeneration based on certain gene-environment interactions (Wilhelm et al, 2008). …”

DNA damage and neurotoxicity of chronic alcohol abuse

“…In adult human chronic alcoholics, brain damage is characterized by cerebral and cerebellar atrophy, and impaired neuronal function within the hippocampus and frontal cortex. 2,3 Besides specific alcohol-related disorders, such as Wernicke–Korsakoff syndrome, hepatic encephalopathy and pellagra, heavy alcohol consumers exhibit cognitive and motor impairments, cholinergic deficits and dementia. It is estimated that 50–75% of long-term alcoholics show cognitive impairment and structural damage to the brain, making chronic alcoholism the second leading cause of dementia behind Alzheimer’s disease.…”

Brain DNA damage and behavioral changes after repeated intermittent acute ethanol withdrawal by young rats

“…Neither the mechanisms underlying the escalation of drinking under intermittent ethanol access nor the exact relevance of such toxicity regarding different brain areas are fully described. The brain is a major target of ethanol, and in adult alcoholics, the brain damage is characterized by cerebral and cerebellar atrophy, and hippocampus and pre-frontal cortex neuronal losses (Harper 1998;Bleich et al 2003). Some authors have demonstrated that ethanol leads to neuronal loss in different brain regions and neuronal loss seems to be associated with cognitive impairment and dementia, neurotransmitter deficiency and mental health issues (Brooks 1997;Brooks 2000;Harper and Matsumoto 2005).…”