Plasma apolipoprotein J as a potential biomarker for Alzheimer's disease: Australian Imaging, Biomarkers and Lifestyle study of aging

Gupta, Veer; Doecke, James D.; Hone, Eugene; Pedrini, Steve; Laws, Simon M.; Thambisetty, Madhav; Bush, Ashley I.; Rowe, Christopher C.; Villemagne, Victor L.; Ames, David; Masters, Colin L.; Macaulay, S. Lance; Rembach, Alan; Martins, Ralph N.

doi:10.1016/j.dadm.2015.12.001

Cited by 32 publications

(26 citation statements)

References 24 publications

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“…Martins et al[33] examined baseline and 18-month follow-up plasma ApoJ (aka clusterin) concentrations in the AIBL cohort. The authors found that ApoJ levels were significantly higher among MCI and AD cases at both time-points and were also correlated with standardized uptake value ratio (SUVR) PET amyloid levels and hippocampal volume.…”

Section: Current State Of the Sciencementioning

confidence: 99%

Blood‐based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic

O’Bryant

Mielke

Rissman

et al. 2016

Alzheimer's & Dementia

250

226

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The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer’s disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility as well as an unclear path for moving basic discovery towards clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state-of-the-art. Additionally, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and towards clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional hand-off model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases.

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Section: Current State Of the Sciencementioning

confidence: 99%

Blood‐based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic

O’Bryant

Mielke

Rissman

et al. 2016

Alzheimer's & Dementia

250

226

View full text Add to dashboard Cite

show abstract

“…Previous studies have also revealed associations between the plasma clusterin level and AD severity and entorhinal cortex atrophy 22, 31, 33 . In our study, the plasma clusterin level was significantly higher in patients with AD than in controls, even after adjustment for multiple confounders.…”

Section: Discussionmentioning

confidence: 89%

Plasma biomarkers are associated with agitation and regional brain atrophy in Alzheimer’s disease

Hsu

Lee

Liao

et al. 2017

Sci Rep

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This study investigated the relationships among plasma biomarkers, regional brain atrophy, and clinical symptoms in patients with Alzheimer’s disease (AD; n = 177), mild cognitive impairment (MCI; N = 60) and controls (n = 108). The Mini-Mental Status Examination (MMSE), Clinical Dementia Rating (CDR), and Neuropsychiatric Inventory (NPI) subscales were administered to subjects. Magnetic resonance imaging was performed and medial temporal atrophy (MTA) and posterior atrophy (PA) were assessed visually. We examined associations among cognition, NPI score, plasma β-amyloid (Aβ) and clusterin levels, and regional brain atrophy in patients with AD by regression analysis. The mean MTA score was associated with the plasma Aβ1-42/Aβ1-40 ratio (r = 0.38, p = 0.01) and with MMSE scores (r = 0.43, p < 0.01). The plasma clusterin level was correlated with CDR sum of box and right-side PA scores (r = 0.28, p = 0.01 and r = 0.30, p = 0.03, respectively). Right-side PA scores were correlated significantly with NPI agitation/aggression (r = 0.30, p = 0.03) subscale scores. In conclusion, the plasma ratio of Aβ1-42/Aβ1-40 and clusterin level may be associated with different patterns of regional brain atrophy, which in turn may account for the clinical symptoms in patients with AD.

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“…Blood-based biomarkers have been studied extensively in AD with regards to diagnostics (81–84), risk prediction (85), understanding the complexity of the pathobiology (86, 87). Within the precision medicine area, the primary need is for companion diagnostic assays (CDx) that not only aid in the identification of which patients are most likely to respond to specific interventions, but also to rule out those patients who may suffer from safety and tolerability issues (75).…”

Section: Discovery Development and Validation Of Pathophysiologicalmentioning

confidence: 99%

Precision Medicine - The Golden Gate for Detection, Treatment and Prevention of Alzheimer’s Disease

Hampel¹,

O’Bryant

Castrillo

et al. 2016

J Prev Alz Dis

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During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer’s disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy. This approach will likely be based on the success found from more advanced research fields, such as oncology. Precision medicine will require integration and transfertilization across fragmented specialities of medicine and direct reintegration of Neuroscience, Neurology and Psychiatry into a continuum of medical sciences away from the silo approach. Precision medicine is biomarker-guided medicine on systems-levels that takes into account methodological advancements and discoveries of the comprehensive pathophysiological profiles of complex multi-factorial neurodegenerative diseases, such as late-onset sporadic AD. This will allow identifying and characterizing the disease processes at the asymptomatic preclinical stage, where pathophysiological and topographical abnormalities precede overt clinical symptoms by many years to decades. In this respect, the uncharted territory of the AD preclinical stage has become a major research challenge as the field postulates that early biomarker guided customized interventions may offer the best chance of therapeutic success. Clarification and practical operationalization is needed for comprehensive dissection and classification of interacting and converging disease mechanisms, description of genomic and epigenetic drivers, natural history trajectories through space and time, surrogate biomarkers and indicators of risk and progression, as well as considerations about the regulatory, ethical, political and societal consequences of early detection at asymptomatic stages. In this scenario, the integrated roles of genome sequencing, investigations of comprehensive fluid-based biomarkers and multimodal neuroimaging will be of key importance for the identification of distinct molecular mechanisms and signaling pathways in subsets of asymptomatic people at greatest risk for progression to clinical milestones due to those specific pathways. The precision medicine strategy facilitates a paradigm shift in Neuroscience and AD research and development away from the classical “one-size-fits-all” approach in drug discovery towards biomarker guided “molecularly” tailored therapy for truly effective treatment and prevention options. After the long and winding decade of failed therapy trials progress towards the holistic systems-based strategy of precision medicine may finally turn into the new age of scientific and medical success curbing the global AD epidemic.

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Plasma apolipoprotein J as a potential biomarker for Alzheimer's disease: Australian Imaging, Biomarkers and Lifestyle study of aging

Cited by 32 publications

References 24 publications

Blood‐based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic

Blood‐based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic

Plasma biomarkers are associated with agitation and regional brain atrophy in Alzheimer’s disease

Precision Medicine - The Golden Gate for Detection, Treatment and Prevention of Alzheimer’s Disease

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