P3‐173: Apolipoproteins and Apolipoprotein Subtypes in Human Cerebrospinal Fluid and Plasma

Koch, Manja; Furtado, Jeremy; Falk, Kim; Leypoldt, Frank; Mukamal, Kenneth J.; Jensen, Majken K.

doi:10.1016/j.jalz.2016.06.1833

Cited by 2 publications

(2 citation statements)

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“…However, the mechanism of lipid clearance from the brain has been difficult to demonstrate. Data suggest that the pools of APOE in the plasma and cerebrospinal fluid are not functionally linked during neurodegeneration and liver-derived APOE does not cross the blood-brain barrier [107][108][109][110]. However, plasma APOE levels and glucose concentrations in the brain are correlated, suggesting other signals cross the blood-brain barrier to support brain health [109,111].…”

Section: Lipid Clearance Supports Adaptive Homeostasis Limiting Infla...mentioning

confidence: 99%

Upstream lipid and metabolic systems are potential causes of Alzheimer's disease, Parkinson's disease and dementias

2022

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Brain health requires circuits, cells and molecular pathways to adapt when challenged and to promptly reset once the challenge has resolved. Neurodegeneration occurs when adaptability becomes confined, causing challenges to overwhelm neural circuitry. Studies of rare and common neurodegenerative diseases suggest that the accumulation of lipids can compromise circuit adaptability. Using microglia as an example, we review data that suggest increased lipid concentrations cause dysfunctional inflammatory responses to immune challenges, leading to Alzheimer's disease, Parkinson's disease and dementia. We highlight current approaches to treat lipid metabolic and clearance pathways and identify knowledge gaps towards restoring adaptive homeostasis in individuals who are at‐risk of losing cognition.

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Section: Lipid Clearance Supports Adaptive Homeostasis Limiting Infla...mentioning

confidence: 99%

Upstream lipid and metabolic systems are potential causes of Alzheimer's disease, Parkinson's disease and dementias

2022

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“…18 Apo (apolipoprotein) A1 is the primary protein constituent of circulatory HDL, whereas apoE, apoJ, and apoC3 are minor HDL constituents found at 10-fold to 100-fold lower concentrations than apoA1 in the HDL fraction of plasma. 19 Accordingly, HDL can be separated into subtypes that do or do not contain specific apos and that may have differential risk on chronic disease. 20 Our previous work suggests that HDL may not exert anti-inflammatory effects if apoC3 is present on HDL.…”

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confidence: 99%

HDL (High-Density Lipoprotein) Subspecies, Prevalent Covert Brain Infarcts, and Incident Overt Ischemic Stroke: Cardiovascular Health Study

Koch

Aroner

Fitzpatrick

et al. 2022

Stroke

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Background and Purpose: Whether HDL (high-density lipoprotein) is associated with risk of vascular brain injury is unclear. HDL is comprised of many apo (apolipoprotein) species, creating distinct subtypes of HDL. Methods: We utilized sandwich ELISA to determine HDL subspecies from plasma collected in 1998/1999 from 2001 CHS (Cardiovascular Health Study) participants (mean age, 80 years). Results: In cross-sectional analyses, participants with higher apoA1 in plasma and lower apoE in HDL were less likely to have prevalent covert magnetic resonance imaging–defined infarcts: odds ratio for apoA1 Q4 versus Q1, 0.68 (95% CI, 0.50–0.93), and odds ratio for apoE Q4 versus Q1, 1.36 (95% CI, 1.01–1.84). Similarly, apoA1 in the subspecies of HDL that lacked apoC3, apoJ, or apoE was inversely related to covert infarcts, and apoE in the subspecies of HDL that lacked apoC3 or apoJ was directly related to covert infarcts in prospective analyses. In contrast, the concentrations of apoA1 and apoE in the complementary subspecies of HDL that contained these apos were unrelated to covert infarcts. Patterns of associations between incident overt ischemic stroke and apoA1, apoE, and apoA1 and apoE in subspecies of HDL were similar to those observed for covert infarcts but less pronounced. Conclusions: This study highlights HDL subspecies defined by apo content as relevant biomarkers of covert and overt vascular brain injury.

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P3‐173: Apolipoproteins and Apolipoprotein Subtypes in Human Cerebrospinal Fluid and Plasma

Cited by 2 publications

References 0 publications

Upstream lipid and metabolic systems are potential causes of Alzheimer's disease, Parkinson's disease and dementias

Upstream lipid and metabolic systems are potential causes of Alzheimer's disease, Parkinson's disease and dementias

HDL (High-Density Lipoprotein) Subspecies, Prevalent Covert Brain Infarcts, and Incident Overt Ischemic Stroke: Cardiovascular Health Study

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