Background: The diagnosis of Alzheimer's disease (AD) during life remains difficult and a definite diagnosis of AD relies on histopathological confirmation at post-mortem or by cerebral biopsy. It is well known that levels of tau proteins are consistently and significantly increased in the cerebrospinal fluid (CSF) of Alzheimer's patients versus levels in normal controls. However, the sole use of this biochemical marker as a test for AD is hampered by mediocre specificity, since tau concentrations may also be elevated in certain other neurological disorders (OND). Studies of the regional cerebral blood flow (rCBF) are widely performed because of their convenience and usefulness in a variety of neurological disorders. Most studies have reported high diagnostic accuracy for brain perfusion single-photon emission tomography (SPECT) in Alzheimer's disease.
Methods: In order to improve specificity, in this study, correlation of 99mTc-HMPAO SPECT scanning and CSF tau protein levels was made in 117 patients with AD, 67 patients with OND (26 of which had other dementias), and 23 age-matched controls. Means and standard deviations of tau protein levels were 297, 42 +/- 221, 12 in AD patients and 78, 07 +/- 98, 51 in patients with OND (p = 0.0006). No correlation was noted between CSF tau protein levels and age, duration of the disease, and neuropsychological scores of mini-mental state examination (MMSE), Cambridge Cognitive Examination (CAMCOG), and Functional Rating Scale for Symptoms of Dementia (FRSSD).
Findings: There was a bilateral parietal and temporal hypoperfusion in patients with AD in SPECT in comparison to normal subjects (p < 0.05) and there was a statistical correlation between this hypoperfusion and neuropsychological tests, such as MMSE and CAMCOG (p < 0.01). There was no correlation between tau protein levels and hypoperfusion in SPECT.
Interpretation: Conclusively, the correlation between elevated levels of tau proteins and hypoperfusion in SPECT in AD patients therefore cannot improve the specificity of tests in AD and this means that the determination of CSF tau proteins levels is not a specific diagnostic test for AD.
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http://dx.doi.org/10.1177/153331750101600107 | DOI Listing |
PLoS One
January 2025
Washington University School of Medicine, NeuroGenomics and Informatics Center, St. Louis, MO, United States of America.
Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science.
View Article and Find Full Text PDFBackground: The immune system is substantially involved in the development and progression of age-related cognitive decline and Alzheimer's disease (AD).
Method: As genetic and environmental factors interactively impact these conditions, we investigated how risk factors such as APOE genotype, age, and sex influence immune activation markers and AD biomarkers in cerebrospinal fluid (CSF) in elderly individuals enrolled in the Mayo Clinic Study of Aging cohort. Among cognitively unimpaired individuals aged over 65 at the baseline visit (N=298), we measured 365 CSF immune activation markers using the proximity extension assay.
Alzheimers Dement
December 2024
Turner Institute for Brain and Mental Health & School of Psychological Sciences, Monash University, Clayton, VIC, Australia.
Background: Plasma and cerebrospinal (CSF) biomarkers are promising candidates for detecting neuropathology. While CSF biomarkers directly reflect pathophysiological processes within the central nervous system, their requirement for a lumbar puncture is a barrier to their widespread scalability in practice. Therefore, we examined cross-sectional associations of plasma biomarkers of amyloid (Aβ42/Aβ40 and pTau-181), neurodegeneration (Neurofilament Light, NfL), and neuroinflammation (Glial Fibrillary Acidic Protein, GFAP) with brain volume, cognition, and their corresponding CSF levels.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Clinical Neurochemistry Laboratory Sahlgrenska University Hospital, Mölndal, Sweden.
Background: This research introduces a novel method for quantifying aggregated tau in body fluids, specifically cerebrospinal fluid (CSF), aiming to enhance the diagnosis and monitoring of neurodegenerative diseases, with a focus on Alzheimer's disease (AD).
Method: By combining tau protein amplification with a highly sensitive single-molecule array (Simoa) immunoassay using an anti-tau antibody CT19.1 in a homogenous manner, the approach enables precise measurements of tau aggregates in CSF.
Alzheimers Dement
December 2024
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background: The brain's ability to perform a cognitive task is a dynamic process and requires small blood vessels to dilate or constrict in real time to adjust blood flow in a region-specific manner. Cerebrovascular Reactivity (CVR) measures the ability of vessels to react to vasoactive challenges. In this work, we investigated the role of CVR as a possible biomarker in small vessel disease related vascular contributions to cognitive impairment and dementia (VCID), as part of the NINDS-funded MarkVCID study.
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