Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins

Ray, Sandip; Britschgi, Markus; Herbert, Charles; Takeda-Uchimura, Yoshiko; Boxer, Adam L.; Blennow, Kaj; Friedman, Leah; Galasko, Douglas; Jutel, Marek; Karydas, Anna; Kaye, Jeffrey; Leszek, Jerzy; Miller, Bruce L.; Minthon, Lennart; Quinn, Joseph F.; Rabinovici, Gil D.; Robinson, William H.; Sabbagh, Marwan N.; So, Yuen T.; Sparks, David L.; Tabaton, Massimo; Tinklenberg, Jared R.; Yesavage, Jerome A.; Tibshirani, Robert; Wyss‐Coray, Tony

doi:10.1038/nm1653

Cited by 965 publications

(850 citation statements)

References 13 publications

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“…A recent study examining plasma signaling proteins as predictors of AD diagnosis suggested changes in blood may be representative of structural and metabolic changes in the brain, and specific to AD [27]. We have a similar hypothesis for SM and ceramides because the homeostasis of these lipids are critical to both the brain and periphery.…”

Section: Discussionmentioning

confidence: 59%

Serum sphingomyelins and ceramides are early predictors of memory impairment

Mielke¹,

Bandaru²,

Haughey³

et al. 2010

Neurobiology of Aging

165

172

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A blood-based biomarker of Alzheimer's disease (AD) progression could be instrumental in targeting asymptomatic individuals for treatment early in the disease process. Given the direct connection between sphingomyelins (SM), ceramides, and apoptosis, these lipids may be indicators of neurodegeneration and AD progression. Baseline serum SM and ceramides from 100 women enrolled in a longitudinal population-based study were examined as predictors of cognitive impairment. Participants were followed up to 6 visits over 9 years. Baseline lipids, in tertiles, were examined in relation to cross-sectional and incident impairment (<1.5 SD below standard norms) on HVLTimmediate and -delayed memory recall and Trails A and B. SM and ceramides varied in relation to the timing of HVLT-delayed impairment: low levels were associated with cross-sectional impairment; high levels predicted incident impairment in asymptomatic individuals. Lipids were not associated with loss-to-follow-up. Results suggest serum SM and ceramides vary according to the timing of the onset of memory impairment and may be good pre-clinical predictors, or biomarkers, of memory impairment: a deficit observed early in AD pathogenesis.

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Section: Discussionmentioning

confidence: 59%

Serum sphingomyelins and ceramides are early predictors of memory impairment

Mielke¹,

Bandaru²,

Haughey³

et al. 2010

Neurobiology of Aging

165

172

View full text Add to dashboard Cite

show abstract

“…CCL, chemokine that contains a C-C motif; CXCL, chemokine that contains a C-X-C motif; G-CSF, granulocyte-colony stimulating factor; GDNF, glialderived neurotrophic factor; ICAM-1, intercellular adhesion molecule-1; IGFBP-1, insulin-like growth factor-binding protein-6; IL, interleukin; PDGF-BB, platelet-derived growth factor BB; TRAIL-R4, TNF-related apoptosis-inducing ligand receptor-4 [15]. Some of these results were verified independently, showing an increased concentration in Biocoll isolated plasma of 5 out of these proteins in MCI and AD patients compared to healthy subjects: EGF, GDNF and MIP1δ (in AD), MIP4 (in MCI), and RANTES (in MCI and AD) [16].…”

Section: Blood Biomarkersmentioning

confidence: 99%

Specific protein biomarker patterns for Alzheimer’s disease: improved diagnostics in progress

Gozes

2017

EPMA Journal

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This short review looks at Alzheimer's disease (AD) diagnosis through my own point of view, going from imaging through cerebrospinal fluid to blood proteins. Over the last couple of years, we have published two papers targeted at Alzheimer's diagnosis. In one paper, we took an approach of selecting a specific target, namely, activitydependent neuroprotective protein (ADNP), and our results tightened the association of ADNP blood expression with intelligence. In another paper, we took an unbiased approach of analysis of all genes expressed in lymphoblastoid cells lines and discovered changes in expression of the regulator of G-protein signaling 2 (RGS2) as a potential AD predictor. This review will assess our data in comparison to selected independent studies focusing on blood protein biomarkers as well as assessing saliva and urine samples with potential predictive value for AD. Furthermore, the review will provide directions for a combination of innovative markers, stratifying the population toward disease prevention and personalized medicine.

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“…While this is likely true, there are cautions that need to be considered with respect to this approach, as well. Among the most promising biomarkers at present include quantitative measures on MRI, cerebrospinal fluid (CSF) markers for tau and Aβ, genetic susceptibilities such as those found with apolipoprotein E genotypes, FDG-PET metabolism patterns, plasma markers for Aβ ratios and proteomic signatures, and molecular imaging such as amyloid imaging with Pittsburgh Compound B (PiB) [10,11,12,13,14,15]. It makes intuitive sense that one or more of these markers coupled with a clinical phenotype may prove very useful.…”

Section: Prediction Modelsmentioning

confidence: 99%

Challenges in clinical research on Alzheimer's disease: Leon Thal's legacy

Petersen

2007

Alzheimer's & Dementia

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First and foremost, Leon Thal was a clinician. While he was an expert in clinical trials and a superb basic scientist, he was primarily a clinical neurologist. As such, Leon had a real appreciation for clinical diagnoses and the implications of them for patients and families.Leon was keenly aware of the importance or moving the diagnostic threshold for Alzheimer's disease (AD) to earlier stages, since it was his belief that, if truly disease-modifying therapies were to be beneficial, they would need to be instituted at an early point in the disease process. This ultimately would have implications for treating asymptomatic individuals.Leon was an early proponent of the concept of mild cognitive impairment (MCI) as a means of identifying individuals at high risk for developing clinical AD at an earlier point in the clinical spectrum. He recognized MCI as the next step for improving our clinical acumen to identify individuals who were going to develop the full picture of AD. Hence, he endorsed and supported the first clinical trial designed to investigate the utility of therapeutics prior to the clinical diagnosis of AD [1].

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Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins

Cited by 965 publications

References 13 publications

Serum sphingomyelins and ceramides are early predictors of memory impairment

Serum sphingomyelins and ceramides are early predictors of memory impairment

Specific protein biomarker patterns for Alzheimer’s disease: improved diagnostics in progress

Challenges in clinical research on Alzheimer's disease: Leon Thal's legacy

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