Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer’s Disease

Sattlecker, Martina; Khondoker, Mizanur; Proitsi, Petroula; Williams, Stephen; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Dobson, Richard

doi:10.3233/jad-140669

Cited by 33 publications

(27 citation statements)

References 54 publications

(62 reference statements)

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“…Further to case-control studies, blood-based biomarker panels have been designed to estimate disease-related phenotypes, such as cognitive decline, brain atrophy and neocortical Aβ deposition. Inflammatory markers [50][51][52], as well as proteins associated with the complement cascade [53], have reported associations with cognitive performance, cognitive decline and clinical progression. Most of these contributions also examined the association of proteomic signatures with brain volumetry finding similar signatures [50,[54][55][56].…”

Section: Panels Of Blood-based Biomarker-associated Disease Phenotypesmentioning

confidence: 99%

Blood-based molecular biomarkers for Alzheimer’s disease

2019

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A major barrier to the effective conduct of clinical trials of new drug candidates against Alzheimer's disease (AD) and to identifying patients for receiving future disease-modifying treatments is the limited capacity of the current health system to find and diagnose patients with early AD pathology. This may be related in part to the limited capacity of the current health systems to select those people likely to have AD pathology in order to confirm the diagnosis with available cerebrospinal fluid and imaging biomarkers at memory clinics. In the current narrative review, we summarize the literature on candidate blood tests for AD that could be implemented in primary care settings and used for the effective identification of individuals at increased risk of AD pathology, who could be referred for potential inclusion in clinical trials or future approved treatments following additional testing. We give an updated account of blood-based candidate biomarkers and biomarker panels for AD-related brain changes. Our analysis centres on biomarker candidates that have been replicated in more than one study and discusses the need of further studies to achieve the goal of a primary care-based screening algorithm for AD.

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Section: Panels Of Blood-based Biomarker-associated Disease Phenotypesmentioning

confidence: 99%

Blood-based molecular biomarkers for Alzheimer’s disease

2019

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“…More recently we have tested protein changes associated with rate of change and progression to dementia [ 55 ] in 235 subjects including 69 controls, 37 ‘stable’ MCI patients, 39 patients with MCI converting to AD within a year, and 90 AD patients. Results showed that twelve proteins were found to significantly associate with the rate of progression.…”

Section: Early Discovery Of Blood-based Biomarkers Of Alzheimer’s Dismentioning

confidence: 99%

A Decade of Blood Biomarkers for Alzheimer’s Disease Research: An Evolving Field, Improving Study Designs, and the Challenge of Replication

Shi

Baird

Westwood

et al. 2018

JAD

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Blood-based biomarkers represent a less invasive and potentially cheaper approach for aiding Alzheimer’s disease (AD) detection compared with cerebrospinal fluid and some neuroimaging biomarkers. Acknowledging that many in the field have made great progress, here we review some of the work that our group has pursued to identify and validate blood-based proteomic biomarkers through both case control and AD pathology endophenotype-based approaches. Our focus is primarily to identify a minimally invasive and hopefully cost-effective blood-based biomarker to reduce screen failure in clinical trials where participants have prodromal or even pre-clinical disease. We summarize some of the key findings and approaches taken in these biomarker studies, while addressing the main challenges, including that of limited replication in the field, and discuss opportunities for biomarker development.

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“…Still, others have found no significant relationship [25,26]. Reduced plasma Ab has also been linked to poorer cognition [6,7,19,21,[27][28][29][30]. In addition, some studies have suggested that plasma levels of Ab42 and Ab40 are associated with the levels of cerebral Ab on positron emission tomography (PET), cerebrospinal fluid levels of Ab and tau, and AD-like brain atrophy [4,7,8,11,16,17,24,[31][32][33][34][35][36][37][38], while others have not seen such an association [25,39,40].…”

Section: Introductionmentioning

confidence: 99%

Plasma amyloid beta levels are associated with cerebral amyloid and tau deposition

Risacher

Fandos

Romero

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction We investigated the relationship of plasma amyloid beta (Aβ) with cerebral deposition of Aβ and tau on positron emission tomography (PET). Methods Forty-four participants (18 cognitively normal older adults [CN], 10 mild cognitive impairment, 16 Alzheimer's disease [AD]) underwent amyloid PET and a blood draw. Free and total plasma Aβ40 and Aβ42 were assessed using a validated assay. Thirty-seven participants (17 CN, 8 mild cognitive impairment, 12 AD) also underwent a [ 18 F]flortaucipir scan. Scans were preprocessed by standard techniques, and mean global and regional amyloid and tau values were extracted. Free Aβ42/Aβ40 (Aβ F42:F40) and total Aβ42/Aβ40 (Aβ T42:T40) were evaluated for differences by diagnosis and relation to PET Aβ positivity. Relationships between these measures and cerebral Aβ and tau on both regional and voxel-wise basis were also evaluated. Results Lower Aβ T42:T40 was associated with diagnosis and PET Aβ positivity. Lower plasma Aβ T42:T40 ratios predicted cerebral Aβ positivity, both across the full sample and in CN only. Finally, lower plasma Aβ T42:T40 ratios were associated with increased cortical Aβ and tau in AD-related regions on both regional and voxel-wise analyses. Discussion Plasma Aβ measures may be useful biomarkers for predicting cerebral Aβ and tau. Additional studies in larger samples are warranted.

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Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer’s Disease

Cited by 33 publications

References 54 publications

Blood-based molecular biomarkers for Alzheimer’s disease

Blood-based molecular biomarkers for Alzheimer’s disease

A Decade of Blood Biomarkers for Alzheimer’s Disease Research: An Evolving Field, Improving Study Designs, and the Challenge of Replication

Plasma amyloid beta levels are associated with cerebral amyloid and tau deposition

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