Co-localization of cholesterol, apolipoprotein E and fibrillar Aβ in amyloid plaques

Burns, Mark P.; Noble, Wendy; Olm, Vicki; Gaynor, Kate; Casey, Evelyn; LaFrancois, John; Wang, Lili; Duff, Karen

doi:10.1016/s0169-328x(02)00647-2

Cited by 115 publications

(81 citation statements)

References 27 publications

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“…Cholesterol and AD pathogenesis Ab, apoE, cholesterol, and cholesterol oxidase have been shown to co-localize in the core of fibrillar plaques in transgenic mice models of AD, 46,47 supporting the suggestion that cholesterol and apoE are involved in fibrillar plaque formation. 47. Cholesterol may be directly involved in Ab aggregation: abnormal oxidative metabolites such as cholesterol-derived aldehydes can modify Ab, firstly promoting Schiff base formation, then accelerating the early stages of amyloidogenesis.…”

Section: Cholesterol and Cad As Ad Risk Factorsmentioning

confidence: 74%

Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease

et al. 2006

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High fat diets and sedentary lifestyles are becoming major concerns for Western countries. They have led to a growing incidence of obesity, dyslipidemia, high blood pressure, and a condition known as the insulin-resistance syndrome or metabolic syndrome. These health conditions are well known to develop along with, or be precursors to atherosclerosis, cardiovascular disease, and diabetes. Recent studies have found that most of these disorders can also be linked to an increased risk of Alzheimer's disease (AD). To complicate matters, possession of one or more apolipoprotein E e4 (APOE e4) alleles further increases the risk or severity of many of these conditions, including AD. ApoE has roles in cholesterol metabolism and Ab clearance, both of which are thought to be significant in AD pathogenesis. The apparent inadequacies of ApoE e4 in these roles may explain the increased risk of AD in subjects carrying one or more APOE e4 alleles. This review describes some of the physiological and biochemical changes that the above conditions cause, and how they are related to the risk of AD. A diversity of topics is covered, including cholesterol metabolism, glucose regulation, diabetes, insulin, ApoE function, amyloid precursor protein metabolism, and in particular their relevance to AD. It can be seen that abnormal lipid, cholesterol and glucose metabolism are consistently indicated as central in the pathophysiology, and possibly the pathogenesis of AD. As diagnosis of mild cognitive impairment and early AD are becoming more reliable, and as evidence is accumulating that health conditions such as diabetes, obesity, and coronary artery disease are risk factors for AD, appropriate changes to diets and lifestyles will likely reduce AD risk, and also improve the prognosis for people already suffering from such conditions.

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Section: Cholesterol and Cad As Ad Risk Factorsmentioning

confidence: 74%

Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease

et al. 2006

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“…We were able to visualize the SPs using a rapid immunohistochemistry technique without pretreatment. The frozen brain sections were thawed for a few minutes at room temperature and incubated for 30 min at room temperature in a 200 l solution containing 5 g/ml of monoclonal 6F/3D antibody (specifi c for the A ␤ peptide epitope amino acids [8][9][10][11][12][13][14][15][16][17]. The samples were then washed three times for 5 min with TBS.…”

Section: Immunohistochemistry Preceding the Microdissectionmentioning

confidence: 99%

“…The samples were then washed three times for 5 min with TBS. Secondary biotinylated goat anti-mouse antibodies (incubated for 15 min at room temperature) were Both techniques stained the SPs ( 12,13 ). However, the fi lipin staining was not abolished by cholesterol extraction; the SPs were still stained in the absence of cholesterol oxidase, and resorufi n alone was found to stain amyloid.…”

Section: Immunohistochemistry Preceding the Microdissectionmentioning

confidence: 99%

Enrichment of cholesterol in microdissected Alzheimer’s disease senile plaques as assessed by mass spectrometry

Panchal

Loeper

Cossec

et al. 2010

Journal of Lipid Research

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The core of the SP is made of aggregated amyloid-␤ (A ␤ ) peptide. A ␤ peptide is cleaved from a type 1 transmembrane protein, the amyloid protein precursor (APP), by the sequential activities of the ␤ and ␥ secretases. Special staining of microscopic sections from brain samples of AD patients has long suggested that SPs were enriched in lipids ( 5 ). The presence of cholesterol among those lipids is plausible since apolipoprotein E (apoE), a transporter of cholesterol, has been found in the SPs by immunohistochemistry ( 6, 7 ). The apo 4 allele is currently considered as the risk factor best associated with AD ( 8 ). Although the role of cholesterol has remained elusive, a much debated meta-analysis has shown that the use of statins, which inhibit cholesterol synthesis, was associated with a decreased prevalence of AD ( 9, 10 ). In cell cultures, the interaction between APP and cholesterol metabolism has been found so intricate that APP has been considered a sensor modulating the cholesterol content of the cell membrane ( 11 ).Histological studies have apparently confi rmed the cholesterol enrichment of the SPs in transgenic mice and AD patients ( 12 ). Two methods have been used. 1 ) Filipin, a well-known fl uorescent probe of membrane cholesterol, labels the SPs and subsequently resists the photobleaching that rapidly decreases the fl uorescence of the surrounding tissue. 2 ) An enzymatic technique based upon cholesterol oxidase activity was initially devised (and commercialized) for colorometric cholesterol assay (not for histochemistry). It is based on the oxidation of Amplex Red ® (10-acetyl-3,7-dihydroxyphenoxazine) into brightly fl uorescent resorufi n. Press, September 18, 2009 DOI 10.1194 Abbreviations: A ␤ , amyloid-␤ peptide; AD, Alzheimer's disease; apoE, apolipoprotein E; APP, amyloid protein precursor; LCM, laser capture microdissection; LC-MS, liquid chromatography coupled with mass spectrometry; LRP, low density lipoprotein receptor-related protein; SP, senile plaque. Published, JLR Papers in

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“…Furthermore, metabolic imaging and particularly positron emission tomography with 11 C-PIB (a compound that specifically stain amyloid plaques) demonstrate that these amyloid accumulations are observed in subjects without any cognitive alteration (Villemagne, Fodero-Tavoletti et al 2008). Although numerous proteins are associated with amyloid deposits in AD (Buée, Hof et al 1992;Uchihara, Duyckaerts et al 1996;Burns, Noble et al 2003), the major proteinaceous component is the 42 amino acid Aß peptide (Aß 42 ) which is the most hydrophobic form of Aß (Jarrett, Berger et al 1993;Gravina, Ho et al 1995). Nevertheless, it was recently demonstrated that aggregation into amyloid plaques may provide truncated forms of this peptide in the N-terminal (Aß 4-/5-/8-/9-42 ) during the first steps of the disease (Sergeant, Bombois et al 2003;Vanderstichele, De Meyer et al 2005).…”

Section: Neuropathological Hallmark and Physiopathological Pathways Omentioning

confidence: 99%

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

Elmoualij¹,

Dupiereux-Fettweis²,

Seguin³

et al. 2011

The Clinical Spectrum of Alzheimer's Disease -the Charge Toward Comprehensive Diagnostic and Therapeutic Strategies

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Co-localization of cholesterol, apolipoprotein E and fibrillar Aβ in amyloid plaques

Cited by 115 publications

References 27 publications

Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease

Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease

Enrichment of cholesterol in microdissected Alzheimer’s disease senile plaques as assessed by mass spectrometry

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

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