The Relation between Apolipoprotein A-I and Dementia: The Honolulu-Asia Aging Study

University of Hawaiʻi at Mānoa, Honolulu, Hawaii, United States
American Journal of Epidemiology (Impact Factor: 5.23). 06/2007; 165(9):985-92. DOI: 10.1093/aje/kwm027
Source: PubMed

ABSTRACT The association between apolipoproteins and neurodegeneration is unclear. The authors examined the association of dementia with serum levels of apolipoprotein A-I (ApoA-I) alone and in combination with the apolipoprotein E genotype (ApoE). Subjects were Japanese-American men in Hawaii followed since 1965 in the Honolulu Heart Program cohort and the Honolulu-Asia Aging Study. Lipid levels were assessed in 1980-1982. Dementia was diagnosed in 1991-1993, 1994-1996, and 1997-1999 by using a multistep procedure and international guidelines. The sample consisted of 929 men (107 dementia cases). The relation between ApoA-I and dementia was examined by using Cox proportional hazards models adjusted for age, education, and cardiovascular risk factors. Compared with men in the lowest quartile, men in the highest quartile of ApoA-I concentration had a significantly lower risk of dementia (hazard ratio = 0.25, 95% confidence interval: 0.08, 0.78). Compared with men with both risk factors, those with a high ApoA-I concentration and no ApoE epsilon4 had a significantly lower risk of dementia (hazard ratio = 0.21, 95% confidence interval: 0.08, 0.52). Previous work has demonstrated an inverse relation between ApoA-I and cardiovascular disease, and the authors extended these findings to the risk of dementia. These results raise the possibility that different lipoprotein components of cholesterol may be differentially associated with dementia.

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    • "Greater ↑FA was associated with decreases in serum ApoA1 between Time 1 and Time 3 while greater ↓FA was associated with increases in serum ApoA1 (Figure 5). Although low serum ApoA1 levels are believed to increase the risk of dementia [38], [39], their relationship to post-TBI neurodegeneration has yet to be determined. "
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    ABSTRACT: Repetitive head impacts (RHI) sustained in contact sports are thought to be necessary for the long-term development of chronic traumatic encephalopathy (CTE). Our objectives were to: 1) characterize the magnitude and persistence of RHI-induced white matter (WM) changes; 2) determine their relationship to kinematic measures of RHI; and 3) explore their clinical relevance. Prospective, observational study of 10 Division III college football players and 5 non-athlete controls during the 2011-12 season. All subjects underwent diffusion tensor imaging (DTI), physiologic, cognitive, and balance testing at pre-season (Time 1), post-season (Time 2), and after 6-months of no-contact rest (Time 3). Head impact measures were recorded using helmet-mounted accelerometers. The percentage of whole-brain WM voxels with significant changes in fractional anisotropy (FA) and mean diffusivity (MD) from Time 1 to 2, and Time 1 to 3 was determined for each subject and correlated to head impacts and clinical measures. Total head impacts for the season ranged from 431-1,850. No athlete suffered a clinically evident concussion. Compared to controls, athletes experienced greater changes in FA and MD from Time 1 to 2 as well as Time 1 to 3; most differences at Time 2 persisted to Time 3. Among athletes, the percentage of voxels with decreased FA from Time 1 to 2 was positively correlated with several helmet impact measures. The persistence of WM changes from Time 1 to 3 was also associated with changes in serum ApoA1 and S100B autoantibodies. WM changes were not consistently associated with cognition or balance. A single football season of RHIs without clinically-evident concussion resulted in WM changes that correlated with multiple helmet impact measures and persisted following 6 months of no-contact rest. This lack of WM recovery could potentially contribute to cumulative WM changes with subsequent RHI exposures.
    PLoS ONE 04/2014; 9(4):e94734. DOI:10.1371/journal.pone.0094734 · 3.23 Impact Factor
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    • "In addition to its role in lipid homeostasis, apoA-I has been recently shown to exhibit antioxidant and anti-inflammatory properties [5] and to inhibit the aggregation and neurotoxicity of the amyloid-β peptide, the main neurotoxin in Alzheimer's disease [6]. Although the possible association between apolipoproteins and neurodegeneration is unclear, increasing apoA-I concentrations have been reported to correlate with decreasing risk of dementia [7], raising the possibility of a novel role of apoA-I in physiological mechanisms of protection against neurological disorders. "
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    ABSTRACT: Amyloidoses constitute a group of diseases in which soluble proteins aggregate and deposit extracellularly in tissues. Nonhereditary apolipoprotein A-I (apoA-I) amyloid is characterized by deposits of nonvariant protein in atherosclerotic arteries. Despite being common, little is known about the pathogenesis and significance of apoA-I deposition. In this work we investigated by fluorescence and biochemical approaches the impact of a cellular microenvironment associated with chronic inflammation on the folding and pro-amyloidogenic processing of apoA-I. Results showed that mildly acidic pH promotes misfolding, aggregation, and increased binding of apoA-I to extracellular matrix elements, thus favoring protein deposition as amyloid like-complexes. In addition, activated neutrophils and oxidative/proteolytic cleavage of the protein give rise to pro amyloidogenic products. We conclude that, even though apoA-I is not inherently amyloidogenic, it may produce non hereditary amyloidosis as a consequence of the pro-inflammatory microenvironment associated to atherogenesis.
    PLoS ONE 07/2011; 6(7):e22532. DOI:10.1371/journal.pone.0022532 · 3.23 Impact Factor
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    • "Further, three separate studies have shown that the level of apoA-I in the serum of patients affected with neurodegenerative disease is reduced when compared to unaffected age matched individuals (Kuriyama et al., 1994; Kawano et al., 1995; Merched et al., 2000). Further longitudinal studies on apoA-I levels show that low apoA-I levels are a risk factor for the development of dementia (Saczynski et al., 2007). "
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    ABSTRACT: Amyloid fibrils arise from the aggregation of misfolded proteins into highly-ordered structures. The accumulation of these fibrils along with some non-fibrillar constituents within amyloid plaques is associated with the pathogenesis of several human degenerative diseases. A number of plasma apolipoproteins, including apolipoprotein (apo) A-I, apoA-II, apoC-II and apoE are implicated in amyloid formation or influence amyloid formation by other proteins. We review present knowledge of amyloid formation by apolipoproteins in disease, with particular focus on atherosclerosis. Further insights into the molecular mechanisms underlying their amyloidogenic propensity are obtained from in vitro studies which describe factors affecting apolipoprotein amyloid fibril formation and interactions. Additionally, we outline the evidence that amyloid fibril formation by apolipoproteins might play a role in the development and progression of atherosclerosis, and highlight possible molecular mechanisms that could contribute to the pathogenesis of this disease.
    Protein & Cell 02/2011; 2(2):116-27. DOI:10.1007/s13238-011-1013-6 · 3.25 Impact Factor
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