A blood-based predictor for neocortical Aβ burden in Alzheimer’s disease: results from the AIBL study

Burnham, Samantha; Faux, Noel; Wilson, William J.; Laws, Simon M.; Ames, David; Bedő, Justin; Bush, Ashley I.; Doecke, James D.; Ellis, Kathryn A.; Head, Richard; Jones, Gareth; Kiiveri, Harri; Martins, Ralph N.; Rembach, Alan; Rowe, Christopher C.; Salvado, Olivier; Macaulay, S. Lance; Masters, Colin L.; Villemagne, Victor L.

doi:10.1038/mp.2013.40

Cited by 105 publications

(103 citation statements)

References 49 publications

(40 reference statements)

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“…Another study found that a panel of serum proteins has diagnostic value 161 , although the sensitivity and specificity of this test need improvement. Individual blood proteins, including biomarkers of neurodegeneration (such as neurofilament light protein, neuron-specific enolase and heart fatty acid binding protein) and glial activation biomarkers (such as YKL-40 and monocyte chemotactic protein 1) also exhibit potential for AD diagnosis and prognostication [162][163][164][165] .…”

Section: Blood Proteinsmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

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The global burden of Alzheimer disease (AD), already the most common type of dementia, is expected to increase still further owing to population ageing. AD not only causes severe distress for patients and caregivers, but also results in a large economic burden on society. Current major challenges in AD include the lack of reliable biomarkers for its early diagnosis, as well as the lack of effective preventive strategies and treatments 1,2 . Thus, increased understanding of the molecular patho genesis of AD could lead to the development of improved diagnostic and therapeutic strategies.AD is conventionally regarded as a CNS disorder. However, increasing experimental, epidemiological and clinical evidence has suggested that manifestations of AD extend beyond the brain. These systemic alterations might not be simply secondary effects of the cerebral degeneration seen in AD, but could reflect under lying processes linked to progression of the disease. AD pathogenesis is complex, involving abnormal amyloid-β (Aβ) metabolism, tau hyperphosphorylation, oxidative stress, reactive glial and microglial changes, and other pathological events. Given that Aβ is a major hallmark of AD and a fertile area of research in this disease, this Review focuses on the systemic role of Aβ in AD. We discuss the communication between peripheral and central pools of Aβ, and describe interactions between systemic abnormalities and AD pathogenesis in the brain. We review emerging findings of associations between systemic abnormalities and Aβ metabolism, and describe how these associations might interact with or reflect on the central pathways of Aβ production and clearance. On the basis of these findings, we suggest that interactions between the brain and the periphery might have a crucial role in the development and progression of AD. Aβ biogenesis and catabolismA steady accrual of data from laboratories and clinics is providing increasing support for the concept that an imbalance between the production and clearance of Aβ is a very early (and often initiating) factor in AD 3 . Normal metabolism of Aβ and maintenance of the homeostatic balance between Aβ production and clearance is, therefore, essential to maintain brain health. In fact, physiological metabolism of Aβ occurs not only in the brain but also in the periphery, and communication between these regions is possible (FIG. 1). Central and peripheral production of AβAβ is derived from the proteolytic cleavage of amyloid precursor protein (APP), which is expressed not only in brain cells, including neurons, astrocytes and microglia, but also in peripheral organs and tissues, such as the Abstract | Alzheimer disease (AD) is the most common type of dementia, and is currently incurable; existing treatments for AD produce only a modest amelioration of symptoms. Research into this disease has conventionally focused on the CNS. However, several peripheral and systemic abnormalities are now understood to be linked to AD, and our understanding of how these alterations contribute to AD is becom...

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Section: Blood Proteinsmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

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“…AIBL, ADNI, and AddNeuroMed researchers have identified multiprotein plasma biomarker panels that together seem to identify individuals with pathological brain Ab accumulation with reasonable accuracy (Burnham et al, 2014;Kiddle et al, 2012). The different panels are, however, nonoverlapping, some protein identities are surprising, and additional validation work is needed.…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 97%

Plasma amyloid β—quo vadis?

Zetterberg

2015

Neurobiology of Aging

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“…Several promising blood biomarker candidates have been identified [77][78][79][80], but they all require further validation before their clinical value is fully known. This effort, however, did lead to an incidental observation that anemia may be associated with AD [81].…”

Section: Australian Adnimentioning

confidence: 99%

The Worldwide Alzheimer's Disease Neuroimaging Initiative: An update

Hendrix

Finger²,

Weiner

et al. 2015

Alzheimer's & Dementia

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The Alzheimer's Disease Neuroimaging Initiative (ADNI), launched in 2004, has worked to accelerate drug development by validating imaging and blood/cerebrospinal fluid biomarkers for Alzheimer's disease clinical treatment trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A true public-private partnership, the initiative has set a new standard for data sharing without embargo and for the use of biomarkers in dementia research. The ADNI effort in North America is not the only such effort in the world. The Alzheimer's Association recognized these global efforts and formed Worldwide ADNI (WW-ADNI). By creating a platform for international collaboration and cooperation, WW-ADNI's goals are to harmonize projects and results across geographical regions and to facilitate data management and availability to investigators around the world. WW-ADNI projects include those based in North America, Europe, Japan, Australia, Korea, and Argentina.

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A blood-based predictor for neocortical Aβ burden in Alzheimer’s disease: results from the AIBL study

Cited by 105 publications

References 49 publications

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

Plasma amyloid β—quo vadis?

The Worldwide Alzheimer's Disease Neuroimaging Initiative: An update

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