Disease relevance of AD5

• CONTEXT: Given the similarities between Alzheimer disease and dementia pugilistica, we evaluated the relationship between apolipoprotein E (APOE) genotype and chronic traumatic brain injury (CTBI) in boxers to determine whether there is a genetic susceptibility to the effects of head trauma [1].
• Sleep-disordered breathing occurs in Alzheimer disease patients and increases risks for cardiovascular disease [2].
• Besides its role in cardiovascular diseases, accumulating evidence has suggested that apoE could play a role in neurodegenerative diseases, such as Alzheimer disease [3].
• The apo E 4/4 phenotype has been reported to be present in most elderly people suffering from the Alzheimer disease, and is associated with increased risk of coronary heart disease and Creutzfeld-Jakob disease [4].
• Several lines of evidence have suggested some common genetic risk factors for Alzheimer disease (AD) and Parkinson disease (PD) because there are some overlapping pathologies in these two neurodegenerative diseases [5].

Psychiatry related information on AD5

• OBJECTIVE: To investigate the association between the apolipoprotein E (APOE) genotypes and dementia in patients with stroke, defined as either vascular dementia (VaD) or Alzheimer disease with cerebrovascular disease (AD with CVD) [6].
• Senile dementia with tangles is suggested to be a variant of Alzheimer disease occurring in the oldest-old, but its nosological position within aging disorders of the brain is still controversy [7].
• SETTING: Memory disorders units at Massachusetts General and Brigham and Women's hospitals, Boston. PATIENTS: Sixty individuals (30 men and 30 women; mean +/- SD age, 75.0+/-9.5 years) with probable Alzheimer disease and scores of 20 or less on the information-memory-concentration subscale of the Blessed Dementia Scale [8].
• All patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for either probable or possible Alzheimer disease [9].
• CONCLUSIONS: With careful case-control matching, visual hallucinations in PD are not associated with the pattern seen for patients with Alzheimer disease and visual hallucinations [10].

High impact information on AD5

• Our database provides a powerful tool for deciphering the genetics of Alzheimer disease, and it serves as a potential model for tracking the most viable gene candidates in other genetically complex diseases [11].
• APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy [12].
• Presenilins Form ER Ca(2+) Leak Channels, a Function Disrupted by Familial Alzheimer's Disease-Linked Mutations [13].
• Neurodegenerative disorders with high brain iron include Parkinson disease, Alzheimer disease and several childhood genetic disorders categorized as neuroaxonal dystrophies [14].
• In this respect, HSS may serve as a model for complex neurodegenerative diseases, such as Parkinson disease, Alzheimer disease, Huntington disease and human immunodeficiency virus (HIV) encephalopathy, in which pathologic accumulation of iron in the brain is also observed [15].

Chemical compound and disease context of AD5

• Homocysteine and folate as risk factors for dementia and Alzheimer disease [16].
• Plasma homocysteine levels, cerebrovascular risk factors, and cerebral white matter changes (leukoaraiosis) in patients with Alzheimer disease [17].
• OBJECTIVE: To determine whether the frequency of dopamine receptor genetic variants and APOE alleles in patients with PD with and without chronic visual hallucinations resembles the pattern previously documented in patients with Alzheimer disease [10].
• Plasma phosphatidylcholine docosahexaenoic Acid content and risk of dementia and Alzheimer disease: the framingham heart study [18].
• In this retrospective analysis of 443 Alzheimer disease (AD) patients from a 30-week tacrine trial, change in Alzheimer's Disease Assessment Scale score from baseline to final value was significantly associated with a total serum cholesterol/APOE genotype interaction [19].

Biological context of AD5

• Complete genomic screen in late-onset familial Alzheimer disease. Evidence for a new locus on chromosome 12 [20].
• OBJECTIVE: To examine more closely the association between apolipoprotein E (APOE) genotype and Alzheimer disease (AD) by age and sex in populations of various ethnic and racial denominations [21].
• A second locus for very-late-onset Alzheimer disease: a genome scan reveals linkage to 20p and epistasis between 20p and the amyloid precursor protein region [22].
• The allele frequency of the APOE-epsilon 4 in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 +/- 0.06; the allele frequency of APOE-epsilon 4 in 91 age-matched unrelated controls was 0.16 +/- 0.03 (Z = 2.44, P = 0.014) [23].
• Gene dosage of the apolipoprotein E (APOE) epsilon 4 allele is a major risk factor for familial Alzheimer disease (AD) of late onset (after age 60) [24].

Anatomical context of AD5

• Neuropathological examination revealed Lewy bodies in all patients, while 1 patient from each family also met the neuropathological criteria for Alzheimer disease [25].
• Apolipoprotein E is immunochemically localized to the senile plaques, vascular amyloid, and neurofibrillary tangles of Alzheimer disease [23].
• OBJECTIVE: To evaluate cerebrospinal fluid (CSF) levels of amyloid beta protein ending at amino acid 42 (Abeta42) and tau as markers for Alzheimer disease (AD) and to determine whether clinical variables influence these levels [26].
• CONCLUSIONS: The APOE epsilon4 allele does not determine medial temporal lobe atrophy or white matter lesions, as measured by magnetic resonance imaging in patients with Alzheimer disease, vascular dementia, or dementia with Lewy bodies [27].
• Several recent studies have asked whether apolipoprotein E (apoE for the protein, APOE for the gene) influences these aspects of specific neuromuscular disorders, as it does in central nervous system disorders such as Alzheimer disease [28].

Associations of AD5 with chemical compounds

• Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease [29].
• (2) Familial defective apolipoprotein B-100 results from a single amino acid substitution in apolipoprotein B that prevents low-density lipoprotein from binding normally to the low-density lipoprotein receptor and elevates plasma cholesterol levels [30].
• CONTEXT: Oxidative processes have been suggested as elements in the development of Alzheimer disease (AD), but whether dietary intake of vitamin E and other antioxidant nutrients prevents its development is unknown [31].
• CONCLUSION: High dietary intake of vitamin C and vitamin E may lower the risk of Alzheimer disease [32].
• BACKGROUND: Apolipoprotein(a) [apo(a)], the distinctive, highly polymorphic glycoprotein of lipoprotein(a), shares a series of common features with apolipoprotein E (apoE), which is implicated in the development of Alzheimer disease [33].

Physical interactions of AD5

• BS69 was first identified as a protein that interacts directly with the transactivation domain (conserved region 3) of the 289R adenovirus type 5 E1A protein [34].
• The Alzheimer disease-related calcium-binding protein Calmyrin is present in human forebrain with an altered distribution in Alzheimer's as compared to normal ageing brains [35].
• Basic fibroblast growth factor binding is a marker for extracellular neurofibrillary tangles in Alzheimer disease [36].
• We have shown previously that the E1B 55-kDa protein (E1B-55 kDa) of adenovirus type 5 (Ad5) binds and inactivates p53 but not p73 [37].
• We previously reported the isolation and functional characterization of seven adenovirus type 5 (Ad5) DNA-binding protein (DBP) point mutants (Quinn, C. O., and Kitchingman, G. R. (1986) J. Virol. 60, 653-661) [38].

Enzymatic interactions of AD5

• Alzheimer Disease-specific Conformation of Hyperphosphorylated Paired Helical Filament-Tau Is Polyubiquitinated through Lys-48, Lys-11, and Lys-6 Ubiquitin Conjugation [39].
• We have used both biochemical and genetic approaches to show that this 496-residue (496R) protein of adenovirus type 5 is phosphorylated at serine and threonine residues near the carboxy terminus within sequences characteristic of substrates of casein kinase II [40].

Co-localisations of AD5

• While apolipoprotein E (ApoE) and beta-amyloid (A beta) co-localize in senile plaques in cortex and cerebellum in Alzheimer disease (AD), the A beta-positive, predominantly diffuse plaques in the striatum do not exhibit ApoE immunoreactivity regardless of disease duration [41].

Regulatory relationships of AD5

• Exceptional advances have been made in understanding the genetics of how common polymorphisms of the apolipoprotein E gene influence the risk and age of onset of Alzheimer disease (AD) [42].
• Tumor necrosis factor (TNF) is an important proinflammatory cytokine that is upregulated in Alzheimer disease (AD) patients and involved with AD genes [43].
• Genetic variation in a haplotype block spanning IDE influences Alzheimer disease [44].
• Compounds that bind APP and inhibit Abeta processing in vitro suggest a novel approach to Alzheimer disease therapeutics [45].
• Furthermore, we show that the PS1-ubiquilin 1 interaction can be detected between endogenous proteins in primary neurons in vitro as well as in brain tissue of healthy controls and Alzheimer disease patients, providing evidence of its physiological relevance [46].

Other interactions of AD5

• No association between butyrylcholinesterase K-variant and Alzheimer disease in Chinese [47].
• Binding of beta/A4 peptide by oxidized apoE may determine the sequestration or targeting of either apoE or beta/A4 peptide, and isoform-specific differences in apoE binding or oxidation may be involved in the pathogenesis of the intra- and extracellular lesions of Alzheimer disease [48].
• The gene encoding nicastrin, a major gamma-secretase component, modifies risk for familial early-onset Alzheimer disease in a Dutch population-based sample [49].
• The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between {beta}-amyloid production and tau phosphorylation in Alzheimer disease [50].
• Thus, the impairment of apoE receptor-dependent neuromodulation may contribute to cognitive impairment and synaptic loss in Alzheimer disease [51].

Analytical, diagnostic and therapeutic context of AD5

• Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database [11].
• The role of heredity in late-onset Alzheimer disease and vascular dementia. A twin study [52].
• Genetic dissection of Alzheimer disease, a heterogeneous disorder [53].
• Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease [54].
• PCR/restriction-enzyme analysis in chimpanzees revealed an APOE profile similar to the human APOE type 4 allele associated with an increased risk of Alzheimer disease [55].

References