A Blood-Based Algorithm for the Detection of Alzheimer’s Disease

Abstract

Background: We previously created a serum-based algorithm that yielded excellent diagnostic accuracy in Alzheimer’s disease. The current project was designed to refine that algorithm by reducing the number of serum proteins and by including clinical labs. The link between the biomarker risk score and neuropsychological performance was also examined. Methods: Serum-protein multiplex biomarker data from 197 patients diagnosed with Alzheimer’s disease and 203 cognitively normal controls from the Texas Alzheimer’s Research Consortium were analyzed. The 30 markers identified as the most important from our initial analyses and clinical labs were utilized to create the algorithm. Results: The 30-protein risk score yielded a sensitivity, specificity, and AUC of 0.88, 0.82, and 0.91, respectively. When combined with demographic data and clinical labs, the algorithm yielded a sensitivity, specificity, and AUC of 0.89, 0.85, and 0.94, respectively. In linear regression models, the biomarker risk score was most strongly related to neuropsychological tests of language and memory. Conclusions: Our previously published diagnostic algorithm can be restricted to only 30 serum proteins and still retain excellent diagnostic accuracy. Additionally, the revised biomarker risk score is significantly related to neuropsychological test performance.

Activity-dependent neuroprotector homeobox protein: A candidate protein identified in serum as diagnostic biomarker for Alzheimer's disease

“…The major lesions associated with AD are amyloid plaques and neurofibrillary tangle formation. Previous studies have also indicated some candidate screening biomarkers for AD such as tau and phosphorylated tau in saliva [8], and α-2-macroglobulin, amyloid, and apolipoproteins in serum [9][10][11]. The most reproducible findings were decreased expression of β-amyloid 1-42 and increased expression of tau and phospho-tau (ptau-181) in CSF samples [6,8,[12][13][14].…”

“…It is important to develop a reliable and accurate clinical blood test method for AD. In previous studies, blood-or serum-based biomarkers for the detection of AD were reported [7][8][9][10][11]14,16]. Blood-based biomarkers are possible and plausible, but more work has to be done to carefully examine the design of studies, the collection and accessibility of cohorts and samples, and the use of technologies [7].…”

Serum-based Protein Profiles of Alzheimer’s Disease and Mild Cognitive Impairment in Elderly Hispanics

“…In the current study, 5 of the top 10 AD markers (I309, IL-5, TN-C, IL-7 and CRP) overlapped with the top 10 markers from our recently cross-validated 21 serum-based biomarker panel [18]. An additional 4 biomarkers of the top 10 AD markers (THPO, eotaxin 3, TN-C, and IL-7) overlapped with the top 10 markers among 30 markers associated with AD among non-Hispanic whites [16]. In contrast, Panamanians and US Mexican Americans have one marker (B2M) in common among the top 10 markers of AD.…”

“…Evidence shows that brain imaging and cerebrospinal fluid biomarkers are highly accurate in detecting disease presence; however, these methods are not cost-and time-effective strategies for primary care clinical settings particularly in low-resource settings. In this regard, recent research into blood-based biomarkers of AD has produced encouraging results that suggest that blood-based screening is a viable approach to early diagnosis [13][14][15][16][17][18][19][20]. Together, the results of these studies provide strong evidence that a blood-based screening approach can be useful in discriminating AD from healthy controls as well as from other dementias [21].…”

Disruption of Neurosynaptic Physiology and Neuron Network Dysfunction in Brain Disorders: An Environmental and Occupational Health Perspective

“…This protein does not have sulph-hydryl group to scavenge heavy metals like mercury. Over-production of Ab may associate arsenic induced inflammatory response and oxidative stress in brain [177,178]. Lead is most potent Ab inducer, followed by cadmium and minor arsenic effect.…”