Cerebrospinal fluid biomarkers for neuropsychological symptoms in early stage of late-onset Alzheimer's disease

Identifying biomarkers that distinguish Parkinson's disease (PD) from normal control (NC) individuals has the potential to increase diagnostic sensitivity for the detection of early-stage PD. A previous proteomic study identified potential biomarkers in postmortem ventricular cerebrospinal fluid (V-CSF) from neuropathologically diagnosed PD subjects lacking Alzheimer's disease (AD) neuropathology. In the present study, we assessed these biomarkers as well as p-tau181, Aβ42, and S100B by ELISA in PD (n = 43) and NC (n = 49) cases. The p-tau181/Aβ42 ratio and ApoA-1 showed statistically significant differences between groups. Multiple regression analysis demonstrated that p-tau181/Aβ42 had a significant odds ratio: OR = 1.42 (95% confidence interval [CI], 1.12–1.84), P = 0.006. Among the molecules investigated, intriguing correlations were observed that require further investigation. Our results suggest coexistent AD CSF biomarkers within the PD group notwithstanding that it was selected to minimize AD neuropathological lesions.

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Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.01.012 ◽

2018 ◽

Vol 14 (7) ◽

pp. 869-879 ◽

Cited By ~ 50

Author(s):

Courtney L. Sutphen ◽

Lena McCue ◽

Elizabeth M. Herries ◽

Chengjie Xiong ◽

Jack H. Ladenson ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Late Onset ◽

Neuronal Injury ◽

Cerebrospinal Fluid Biomarkers

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“Brain Fog” by COVID-19 or Alzheimer’s Disease? A Case Report

Frontiers in Psychology ◽

10.3389/fpsyg.2021.724022 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jordi A. Matias-Guiu ◽

Cristina Delgado-Alonso ◽

Miguel Yus ◽

Carmen Polidura ◽

Natividad Gómez-Ruiz ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Older Patients ◽

Early Stage ◽

Acute Infection ◽

Cognitive Symptoms ◽

Cerebrospinal Fluid Biomarkers ◽

Detailed Assessment ◽

Underlying Mechanisms

Cognitive symptoms after COVID-19 have been increasingly recognized several months after the acute infection and have been designated as “brain fog.” We report a patient with cognitive symptoms that started immediately after COVID-19, in which cerebrospinal fluid biomarkers were highly suggestive of Alzheimer’s disease. Our case highlights the need to examine patients with cognitive symptoms following COVID-19 comprehensively. A detailed assessment combining clinical, cognitive, and biomarker studies may help disentangle the underlying mechanisms associated with cognitive dysfunction in each case. The investigation of neurodegenerative processes in an early stage, especially in older patients, is probably warranted.

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Faculty Opinions recommendation of Cerebrospinal fluid biomarkers and cerebral atrophy in distinct clinical variants of probable Alzheimer's disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725508178.793507921 ◽

2015 ◽

Author(s):

Martin Rossor ◽

Jonathan Rohrer

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cerebral Atrophy ◽

Cerebrospinal Fluid Biomarkers ◽

Clinical Variants

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Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer’s disease

Translational Psychiatry ◽

10.1038/s41398-021-01218-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hao Hu ◽

Lan Tan ◽

Yan-Lin Bi ◽

Wei Xu ◽

Lin Tan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Peripheral Blood ◽

Late Onset ◽

Early Stage ◽

Susceptibility Gene ◽

Subjective Cognitive Decline ◽

Preclinical Ad ◽

T Tau ◽

New Evidence

AbstractThe bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer’s disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aβ42 (p = 0.0008), as well as increased p-tau/Aβ42 (p = 0.0001) and t-tau/Aβ42 (p < 0.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of BIN1 promoter was also accompanied by increased CSF p-tau (p = 0.0028) and t-tau (p = 0.0130) in the SCD subgroup, which was independent of CSF Aβ42. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of APOE ɛ4 status. Our study is the first to find a robust association between hypomethylation of BIN1 promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of BIN1 in AD, and may contribute to the discovery of new therapeutic targets for AD.

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Unique Sleep and Circadian Rhythm Dysfunction Neuroinflammatory and Immune Profiles in Alzheimer’s Disease with Mild Cognitive Impairment

Journal of Alzheimer s Disease ◽

10.3233/jad-201573 ◽

2021 ◽

pp. 1-6

Author(s):

Jagan A. Pillai ◽

James Bena ◽

Lynn M. Bekris ◽

Nancy Foldvary-Schaefer ◽

Catherine Heinzinger ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Circadian Rhythm ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Cerebrospinal Fluid Biomarkers ◽

Circulating Markers

Sleep dysfunction has been identified in the pathophysiology of Alzheimer’s disease (AD); however, the role and mechanism of circadian rhythm dysfunction is less well understood. In a well-characterized cohort of patients with AD at the mild cognitive impairment stage (MCI-AD), we identify that circadian rhythm irregularities were accompanied by altered humoral immune responses detected in both the cerebrospinal fluid and plasma as well as alterations of cerebrospinal fluid biomarkers of neurodegeneration. On the other hand, sleep disruption was more so associated with abnormalities in circulating markers of immunity and inflammation and decrements in cognition.

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Differential Cued-Stroop Performance in Cognitively Asymptomatic Older Adults with Biomarker-Identified Risk for Alzheimer’s Disease: A Pilot Study

Current Alzheimer Research ◽

10.2174/1567205015666180404170359 ◽

2018 ◽

Vol 15 (9) ◽

pp. 820-827 ◽

Cited By ~ 5

Author(s):

Ryan Van Patten ◽

Anne M. Fagan ◽

David A.S. Kaufman

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Stroop Task ◽

Coefficient Of Variation ◽

Reaction Times ◽

Preclinical Alzheimer’S Disease ◽

Cerebrospinal Fluid Biomarkers ◽

Accuracy Rates

Background: There exists a need for more sensitive measures capable of detecting subtle cognitive decline due to Alzheimer's disease. Objective: To advance the literature in Alzheimer’s disease by demonstrating that performance on a cued-Stroop task is impacted by preclinical Alzheimer's disease neuropathology. Method: Twenty-nine cognitively asymptomatic older adults completed a computerized, cued-Stroop task in which accuracy rates and intraindividual variability in reaction times were the outcomes of interest. Cerebrospinal fluid biomarkers of Aβ42 and tau were measured and participants were then grouped according to a published p-tau/Aβ42 cutoff reflecting risk for Alzheimer’s disease (preclinical Alzheimer's disease = 14; control = 15). Results: ANOVAs indicated that accuracy rates did not differ between the groups but 4-second delay incongruent color-naming Stroop coefficient of variation reaction times were higher in the preclinical Alzheimer’s disease group compared to the control group, reflecting increased within-person variability. Moreover, partial correlations showed no relationships between cerebrospinal fluid biomarkers and accuracy rates. However, increases in coefficient of variation reaction times correlated with decreased Aβ42 and increases in p-tau and the p-tau/Aβ42 ratio. Conclusion: Results supported the ability of the computerized, cued-Stroop task to detect subtle Alzheimer’s disease neuropathology using a small cohort of cognitively asymptomatic older adults. The ongoing measurement of cued-Stroop coefficient of variation reaction times has both scientific and clinical utility in preclinical Alzheimer’s disease.

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Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease

Human Brain Mapping ◽

10.1002/hbm.23897 ◽

2017 ◽

Vol 39 (2) ◽

pp. 971-984 ◽

Cited By ~ 16

Author(s):

Christine L. Tardif ◽

Gabriel A. Devenyi ◽

Robert S. C. Amaral ◽

Sandra Pelleieux ◽

Judes Poirier ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Preclinical Alzheimer’S Disease ◽

Cerebrospinal Fluid Biomarkers ◽

Hippocampal Circuitry

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Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Current Evidence and Future Perspectives

Brain Sciences ◽

10.3390/brainsci11020215 ◽

2021 ◽

Vol 11 (2) ◽

pp. 215

Author(s):

Donovan A. McGrowder ◽

Fabian Miller ◽

Kurt Vaz ◽

Chukwuemeka Nwokocha ◽

Cameil Wilson-Clarke ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Late Onset ◽

Amyloid Β ◽

Current Evidence ◽

Csf Biomarkers ◽

Diagnostic Efficacy ◽

Neurofilament Light ◽

New Biomarkers

Alzheimer’s disease is a progressive, clinically heterogeneous, and particularly complex neurodegenerative disease characterized by a decline in cognition. Over the last two decades, there has been significant growth in the investigation of cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease. This review presents current evidence from many clinical neurochemical studies, with findings that attest to the efficacy of existing core CSF biomarkers such as total tau, phosphorylated tau, and amyloid-β (Aβ42), which diagnose Alzheimer’s disease in the early and dementia stages of the disorder. The heterogeneity of the pathophysiology of the late-onset disease warrants the growth of the Alzheimer’s disease CSF biomarker toolbox; more biomarkers showing other aspects of the disease mechanism are needed. This review focuses on new biomarkers that track Alzheimer’s disease pathology, such as those that assess neuronal injury (VILIP-1 and neurofilament light), neuroinflammation (sTREM2, YKL-40, osteopontin, GFAP, progranulin, and MCP-1), synaptic dysfunction (SNAP-25 and GAP-43), vascular dysregulation (hFABP), as well as CSF α-synuclein levels and TDP-43 pathology. Some of these biomarkers are promising candidates as they are specific and predict future rates of cognitive decline. Findings from the combinations of subclasses of new Alzheimer’s disease biomarkers that improve their diagnostic efficacy in detecting associated pathological changes are also presented.

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Diﬃculties in diagnosing atypical variants of Alzheimer’s disease

Russian neurological Journal ◽

10.30629/2658-7947-2021-26-5-16-23 ◽

2021 ◽

Vol 26 (5) ◽

pp. 16-23

Author(s):

A. A. Tappakhov ◽

T. Ya. Nikolaeva ◽

T. E. Popova ◽

N. A. Shnayder

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Picture ◽

Short Term Memory ◽

Late Onset ◽

Early Stage ◽

Primary Progressive Aphasia ◽

Cortical Atrophy ◽

Posterior Cortical Atrophy ◽

Short Term

Alzheimer’s disease (AD) is the most common cause of dementia in the population. Late onset AD has a classic clinical picture with short-term memory deficit, apraxia and agnosia. Patients with early-onset AD may have an atypical clinical picture which complicates diagnosis. Atypical AD variants include the logopenic variant of primary progressive aphasia, posterior cortical atrophy, behavioral, biparietal, and cortico-basal variants. These variants have pathomorphological signs similar to classical AD, but at an early stage they are characterized by focal atrophy which explains their clinical polymorphism. This article provides a review of the current literature on atypical types of AD and presents a clinical case of a 62-year-old patient in whom the disease debuted with prosopagnosia due to focal atrophy of the temporo-occipital regions of the non-dominant hemisphere.

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