Plasma β Amyloid and the Risk of Alzheimer Disease and Dementia in Elderly Men

Sundelöf, Johan; Giedraitis, Vilmantas; Irizarry, Michael C.; Sundström, Johan; Ingelsson, Erik; Rönnemaa, Elina; Ärnlöv, Johan; Gunnarsson, Malin Degerman; Hyman, Bradley T.; Basun, Hans; Ingelsson, Martin; Lannfelt, Lars; Kilander, Lena

doi:10.1001/archneurol.2007.57

Cited by 104 publications

(77 citation statements)

References 41 publications

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“…[47][48][49] Conversely, low baseline levels of plasma Ab1-40 at age 77 were associated with increased AD risk in men. 50 A lower plasma Ab1-42/Ab1-40 ratio was associated with increased risk for AD over a 3-year follow-up in a longitudinal study of 563 individuals. 51 In the largest longitudinal study to date, the combination of higher baseline Ab1-40 levels and lower Ab1-42 levels was associated with increased risk for dementia over a period of 8-9 years.…”

Section: Plasma Ab As a Diagnostic Markermentioning

confidence: 91%

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

et al. 2008

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Currently, the 'amyloid hypothesis' is the most widely accepted explanation for the pathogenesis of Alzheimer's disease (AD). According to this hypothesis, altered metabolism of the amyloid-b (Ab) peptide is central to the pathological cascade involved in the pathogenesis of AD. Although Ab is produced by almost every cell in the body, a physiological function for the peptide has not been determined, and the pathways by which Ab leads to cognitive dysfunction and cell death are unclear. Numerous therapeutic approaches that target the production, toxicity and removal of Ab are being developed worldwide. Although therapeutic treatment for AD may be imminent, the value and effectiveness of such treatment are largely dependent on early diagnosis of the disease. This review summarizes current knowledge of Ab clearance, transport and degradation, and evaluates the use of such information in the development of diagnostic tools. The conflicting results of plasma Ab ELISAs are discussed, as are the more promising results of Ab imaging by positron emission tomography. Current knowledge of Ab-binding proteins and Ab-degrading enzymes is analysed in the context of a potential therapy for AD. Transport across the blood-brain barrier by the receptor for advanced glycation end products and efflux via the multi-ligand lipoprotein receptor LRP-1 is also reviewed. Enhancing clearance and degradation of Ab remains an attractive therapeutic strategy, and improved understanding of Ab clearance may lead to advances in diagnostics and interventions designed to prevent or delay the onset of AD.

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Section: Plasma Ab As a Diagnostic Markermentioning

confidence: 91%

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

et al. 2008

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“…Similarly, other studies showed that elevated levels of Aβ-42 (van Oijen et al, 2006) low levels of Aβ-40 (Sundelof et al, 2008) or a reduced Aβ-42/Aβ-40 ratio in plasma (Graff-Radford et al, 2007) in aging could indicate the conversion from a normal cognitive status to MCI or AD. In contrast, others reported that reduced Aβ-42 plasma levels might reflect the evolution from normal aging or MCI to AD (Song et al, 2007), rather than a marker for neuropathological events occurring in the disease.…”

Section: Biomarkers In Plasmamentioning

confidence: 80%

Biomarkers for Alzheimer’s disease and other forms of dementia: Clinical needs, limitations and future aspects

Cedazo-Minguez

Winblad

2010

Experimental Gerontology

137

133

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To cite this version:Angel Cedazo-Minguez, Bengt Winblad. Biomarkers for Alzheimer's disease and other forms of dementia: clinical needs, limitations and future aspects. Experimental Gerontology, Elsevier, 2009, 45 (1), pp. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT

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“…Increased Ab or Ab 1-42 levels have been shown to predict the development of AD [113,114]; however, other analyses have revealed no associations [115,116] or opposite [117] results. A low Ab 1-42 /Ab 1-40 ratio is assumed to predict future AD [113,118,119].…”

Section: Blood Prospective Candidate Biomarkersmentioning

confidence: 97%

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

Hampel

Lista

Teipel

et al. 2014

Biochemical Pharmacology

105

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Recent advances in understanding the molecular mechanisms underlying various paths toward the pathogenesis of Alzheimer's disease (AD) has begun to provide new insight for interventions to modify disease progression. The evolving knowledge gained from multidisciplinary basic research has begun to identify new concepts for treatments and distinct classes of therapeutic targets; as well as putative disease-modifying compounds that are now being tested in clinical trials. There is a mounting consensus that such disease modifying compounds and/or interventions are more likely to be effectively administered as early as possible in the cascade of pathogenic processes preceding and underlying the clinical expression of AD. The budding sentiment is that "treatments" need to be applied before various molecular mechanisms converge into an irreversible pathway leading to morphological, metabolic and functional alterations that characterize the pathophysiology of AD. In light of this, biological indicators of pathophysiological mechanisms are desired to chart and detect AD throughout the asymptomatic early molecular stages into the prodromal and early dementia phase. A major conceptual development in the clinical AD research field was the recent proposal of new diagnostic criteria, which specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD. This paradigm shift in AD definition, conceptualization, operationalization, detection and diagnosis represents novel fundamental opportunities for the modification of interventional trial designs. This perspective summarizes not only present knowledge regarding biological markers but also unresolved questions on the status of surrogate indicators for detection of the disease in asymptomatic people and diagnosis of AD

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Plasma β Amyloid and the Risk of Alzheimer Disease and Dementia in Elderly Men

Abstract: Background: ␤ Amyloid (A␤) protein accumulates in the brains of individuals with Alzheimer disease (AD) and is detectable in cerebrospinal fluid and plasma.Objective: To examine plasma levels of A␤ peptides A␤ 40 and A␤ 42 as predictors of incident AD and other types of dementia.

Cited by 104 publications

References 41 publications

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

Biomarkers for Alzheimer’s disease and other forms of dementia: Clinical needs, limitations and future aspects

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

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