Dataset Information

Apolipoprotein E, amyloid-beta, and neuroinflammation in Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is characterized by the accumulation and deposition of amyloid-beta (Aβ) peptides in the brain. Neuroinflammation occurs in the AD brain and plays a critical role in the neurodegenerative pathology. Particularly, Aβ evokes an inflammatory response that leads to synaptic dysfunction, neuronal death, and neurodegeneration. Apolipoprotein E (ApoE) proteins are involved in cholesterol transport, Aβ binding and clearance, and synaptic functions in the brain. The ApoE4 isoform is a key risk factor for AD, while the ApoE2 isoform has a neuroprotective effect. However, studies have reached different conclusions about the roles of the isoforms; some show that both ApoE3 and ApoE4 have anti-inflammatory effects, while others show that ApoE4 causes a predisposition to inflammation or promotes an inflammatory response following lipopolysaccharide treatment. These discrepancies may result from the differences in models, cell types, experimental conditions, and inflammatory stimuli used. Further, little was known about the role of ApoE isoforms in the Aβ-induced inflammatory response and in the neuroinflammation of AD. Our recent work showed that ApoE isoforms differentially regulate and modify the Aβ-induced inflammatory response in neural cells, with ApoE2 suppressing and ApoE4 promoting the response. In this article, we review the roles, mechanisms, and interrelations among Aβ, ApoE, and neuroinflammation in AD.

SUBMITTER: Dorey E

PROVIDER: S-EPMC5562666 | biostudies-other | 2014 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:The aim of this longitudinal study was to assess with positron emission tomography (PET) the relationship between levels of inflammation and the loads of aggregated ?-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease. METHODS:Forty-three subjects with mild cognitive impairment (MCI) had serial 11C-PK11195 PET over 2 years to measure inflammation changes, and 11C-PiB PET to determine ?-amyloid fibril load; 22 also had serial 18F-Flortaucipir PET to determine tau tangle load. Cortical surface statistical mapping was used to localise areas showing significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years. RESULTS:Those MCI subjects with high 11C-PiB uptake at baseline (classified as prodromal Alzheimer's disease) had raised inflammation levels which significantly declined across cortical regions over 2 years although their ?-amyloid levels continued to rise. Those MCI cases who had low/normal 11C-PiB uptake at baseline but their levels then rose over 2 years were classified as prodromal AD with low Thal phase 1-2 amyloid deposition at baseline. They showed levels of cortical inflammation which correlated with their rising ?-amyloid load. Those MCI cases with baseline low 11C-PiB uptake that remained stable were classified as non-AD, and they showed no correlated inflammation levels. Finally, MCI cases which showed both high 11C-PiB and 18F-Flortaucipir uptake at baseline (MCI due to AD) showed a further rise in their tau tangle load over 2 years with a correlated rise in levels of inflammation. CONCLUSIONS:Our baseline and 2-year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer's disease: MCI cases with low baseline but subsequently rising ?-amyloid load show correlated levels of microglial activation which then later decline when the ?-amyloid load approaches AD levels. Later, as tau tangles form in ?-amyloid positive MCI cases with prodromal AD, the rising tau load is associated with higher levels of inflammation.

Dataset Information

Apolipoprotein E, amyloid-beta, and neuroinflammation in Alzheimer's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets