Blood-based biomarkers for Alzheimer's disease: towards clinical implementation

Teunissen, Charlotte E.; Verberk, Inge M.W.; Thijssen, Elisabeth H.; Vermunt, Lisa; Hansson, Oskar; Zetterberg, Henrik; Flier, Wiesje M. van der; Mielke, Michelle M.; Campo, Marta Del

doi:10.1016/s1474-4422(21)00361-6

Cited by 556 publications

(575 citation statements)

References 119 publications

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“…Neurofilament light is known to form polymers and it remains to be elucidated what forms are measured with the two platforms. Consistent with the NEFL results on Olink Explore, high NEFL levels in CSF and blood have been reported to associate with advanced Alzheimer’s disease 21 . The opposite effect on SomaScan v4 indicates that the two platforms are either targeting different forms of the same protein, or different proteins entirely.…”

Section: Resultssupporting

confidence: 78%

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Large-scale comparison of immunoassay- and aptamer-based plasma proteomics through genetics and disease

Eldjárn

Ferkingstad

Lund

et al. 2022

Preprint

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High-throughput proteomics platforms measuring thousands of proteins in blood combined with genomic information have the power to bridge the gap between the genome and diseases and in that capture some of the environmental contributions to their risk and pathogenesis. Although such methods have already demonstrated their utility, the validation of their actual protein targets is lacking. Here we present a large-scale analysis of levels of proteins in plasma and protein quantitative trait loci (pQTLs) detected using the Olink Explore 1536 (1,459 immunoassays) in 47,151 European participants from the UK Biobank with 57.7 million imputed sequence variants. We compared the results with those of a large-scale SomaScan v4 study (35,559 participants and 4,907 aptamer-based assays) in order to assess and compare the qualities of these two platforms. The correlation between levels of proteins targeted by the two platforms is modest (median Spearman correlation 0.46). The vast majority of assays on the Olink Explore platform had cis pQTLs, evidence that they correctly target their intended proteins (84%), while the assays on the SomaScan v4 platform were half as likely to have cis pQTLs (38%). We also highlight novel pQTLs discovered using the Olink Explore platform, not captured by SomaScan v4, and describe their colocalization with disease-associated sequence variants as well as associations between protein levels and diseases. Our results further underscore the value of proteomics data and highlight the major differences in quality between the two most commonly used high-throughput proteomics platforms.

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Section: Resultssupporting

confidence: 78%

Section: Predicting Disease Phenotypes With Protein Levelssupporting

confidence: 78%

Large-scale comparison of immunoassay- and aptamer-based plasma proteomics through genetics and disease

Eldjárn

Ferkingstad

Lund

et al. 2022

Preprint

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“…746 Some biomarker tests, such as positron emission tomography (PET) imaging to look for beta-amyloid deposits or pathologic tau in the brain and measurement of a type of beta-amyloid called Aβ 42 in CSF are readily available to physicians, whereas others are currently limited to clinical research. 746,747 Unfortunately, not all physicians and patients have access to biomarker testing methods, and not all patients are referred for a more thorough evaluation after MCI is diagnosed based on the symptoms. New blood tests are under development that provide simple, accurate, non-invasive detection of Alzheimer's disease biomarkerssometimes even before symptoms appear.…”

Section: Due To Alzheimer's Disease: a Distinct Conditionmentioning

confidence: 99%

2022 Alzheimer's disease facts and figures

2022

Alzheimer's & Dementia

1,549

664

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This article describes the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality and morbidity, use and costs of care, and the overall impact on family caregivers, the dementia workforce and society. The Special Report discusses consumers' and primary care physicians' perspectives on awareness, diagnosis and treatment of mild cognitive impairment (MCI), including MCI due to Alzheimer's disease. An estimated 6.5 million Americans age 65 and older are living with Alzheimer's dementia today. This number could grow to 13.8 million by 2060 barring the development of medical breakthroughs to prevent, slow or cure AD. Official death certificates recorded 121,499 deaths from AD in 2019, the latest year for which data are available. Alzheimer's disease was officially listed as the sixth-leading cause of death in the United States in 2019 and the seventh-leading cause of death in 2020 and 2021, when COVID-19 entered the ranks of the top ten causes of death. Alzheimer's remains the fifth-leading cause of death among Americans age 65 and older. Between 2000 and 2019, deaths from stroke, heart disease and HIV decreased, whereas reported deaths from AD increased more than 145%. More than 11 million family members and other unpaid caregivers provided an estimated 16 billion hours of care to people with Alzheimer's or other dementias in 2021. These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver. Unpaid dementia caregiving was valued at $271.6 billion in 2021. Its costs, however, extend to family caregivers' increased risk for emotional distress and negative mental and physical health outcomes -costs that have been aggravated by COVID-19. Members of the dementia care workforce have also been affected by COVID-19. As essential care workers, some have opted to change jobs to protect their own health and the health of their families. However, this occurs at a time when more members of the dementia care workforce are needed. Average per-person Medicare payments for services to beneficiaries age 65 and older with AD or other dementias are almost three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 22 times as great. Total payments in 2022 for health care, long-term care and hospice services for people age 65 and older with dementia are estimated to be $321 billion. A recent survey commissioned by the Alzheimer's Association revealed several barriers to consumers' understanding of MCI. The survey showed low awareness of MCI among Americans, a reluctance among Americans to see their doctor after noticing MCI symptoms, and persistent challenges for primary care physicians in diagnosing MCI. Survey results indicate the need to improve MCI 700

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“…Amyloid-β42(Aβ42)/Aβ40 ratio and phosphorylated tau at threonine-181 (p-tau181) in blood have demonstrated to reflect amyloidosis and tauopathy in AD with a reliability similar to what observed in CSF. Also, ongoing neurodegeneration and neuroinflammation can be efficiently quantified by blood neurofilament light chain (NfL) and glial fibrillar acid protein (GFAP), respectively 2…”

Section: A Panel Of Five Plasma Biomarkers Has Shown a Characteristic...mentioning

confidence: 99%