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Abstract: Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer’s disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Here, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n = 388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202/205. These findings support plasma p-tau212 as a peripherally accessible biomarker of AD pathophysiology.
Keywords: plasma p-tau212, diagnostics, Alzheimer disease, neuropathology
Published in DiRROS: 15.06.2026; Views: 158; Downloads: 110
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Abstract: Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases. Their treatment options are rather limited, and no neuroprotective or disease-modifying treatments are available. Anti-diabetic drugs, such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonists, have been suggested as a potential therapeutic option. Aims: Assess GLP1R and GIPR genetic variability in relation to AD- and PD-related phenotypes. Methods: AD, PD patients and healthy control subjects were included in the study. Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease were measured in AD patients, while cognitive impairment was evaluated in PD. All participants were genotyped for three SNPs: GLP1R rs10305420, GLP1R rs6923761 and GIPR rs1800437. Results: GLP1R rs10305420 genotypes were associated with increased odds for AD and PD development. GLP1R rs10305420 and GLP1R rs6923761 genotypes were significantly associated with Aβ42/40 ratio (p = 0.041 and p = 0.050), while GLP1R rs6923761 was also associated with p-tau levels (p = 0.022). Finally, GIPR rs1800437 heterozygotes as well as carriers of at least one GIPR rs1800437 C allele presented with increased odds for the development of dementia in PD (OR = 1.92; 95 % CI = 1.05-3.51; p = 0.034 and OR = 1.95; 95 % CI = 1.08-3.52; p = 0.027, respectively). Conclusion: GLP1R and GIPR genetic variability may affect the occurrence of AD and PD and is also associated with AD CSF biomarkers for Alzheimer's disease and dementia in PD. The data on GLP1R and GIPR genetic variability may support the function of incretin receptors in neurodegeneration.
Keywords: Alzheimer's disease, biomarker, glucagon-like peptide 1 receptor, glucose-dependent insulinotropic polypeptide, Parkinson's disease, polymorphism
Published in DiRROS: 09.06.2026; Views: 162; Downloads: 149
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Abstract: Background Previous research on associations between cardiovascular health, measured at a single timepoint, and rate of age-related cognitive decline shows divergent findings dependent on the participants’ age and the health metric studied. The aim of this study was to add to the knowledge in this field by investigating whether change in cardiovascular health, assessed with Life’s Simple 7 (LS7) score, is associated with rate of cognitive change in youngold and old-old adults. Methods The study included 1022 participants aged≥60 years from the Swedish National Study on Aging and CareKungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic memory, semantic memory, verbal fluency, and perceptual speed) across up to 15 years. LS7, composed of seven cardiovascular health metrics (smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure), was assessed at baseline and at the 6-year follow-up. Change in LS7 was calculated as the difference between baseline and 6 years (range −5 to 8 points) and categorised into worse (−5 to −2 points), stable (−1 to 1 points), and improved (2 to 8 points). Change in cognitive performance as a function of LS7 change categories was estimated using linear mixed-effects models. Results Participants were classified as stable (67.1%), improved (21.0%), or worse (11.8%) according to changes in LS7 score. Both the worse and improved categories were associated with faster cognitive decline. Age-stratified analyses revealed that worsening of LS7 was clearly associated with faster cognitive decline in the old-old (≥78 years), whereas improvement tended be associated with faster cognitive decline in the young-old (<78 years) group. Conclusions Change in cardiovascular health in old age may lead to accelerated cognitive decline, particularly in late senescence. These results suggest that it is important to monitor and maintain cardiovascular health status in very old adults.
Keywords: aging, cardiovascular risk factors, cognition, epidemiology
Published in DiRROS: 04.06.2026; Views: 175; Downloads: 112
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Abstract: Introduction: The established cerebrospinal fluid (CSF) phosphorylated tau181 (p-tau181) may not reliably reflect concomitant Alzheimer's disease (AD) and primary age-related tauopathy (PART) found in Creutzfeldt-Jakob disease (CJD) at autopsy. Methods: We investigated CSF N-terminal p-tau181, p-tau217, and p-tau231 with in-house Simoa assays in definite CJD (n = 29), AD dementia (n = 75), mild cognitive impairment (MCI) due to AD (n = 65), and subjective cognitive decline (SCD, n = 28). Post-mortem examination performed in patients with CJD 1.3 (0.3-14.3) months after CSF collection revealed no co-pathology in 10, concomitant AD in 8, PART in 8, and other co-pathologies in 3 patients. Results: N-terminal p-tau was increased in CJD versus SCD (p < 0.0001) and correlated with total tau (t-tau) in the presence of AD and PART co-pathology (rho = 0.758-0.952, p ≤ 001). Concentrations in CJD+AD were indistinguishable from AD dementia, with the largest fold-change in p-tau217 (11.6), followed by p-tau231 and p-tau181 (3.2-4.5). Discussion: Variable fold-changes and correlation with t-tau suggest that p-tau closely associates with neurodegeneration and concomitant AD in CJD. Highlights: N-terminal phosphorylated tau (p-tau) biomarkers are increased in Creutzfeldt-Jakob disease (CJD) with and without concomitant AD. P-tau217, p-tau231, and p-tau181 correlate with total tau (t-tau) and increase in the presence of amyloid beta (Aβ) co-pathology. N-terminal p-tau181 and p-tau231 in Aβ-negative CJD show variation among PRNP genotypes. Compared to mid-region-targeting p-tau181, cerebrospinal fluid (CSF) N-terminal p-tau has greater potential to reflect post-mortem neuropathology in the CJD brain.
Keywords: Alzheimer's disease, Creutzfeldt–Jakob disease, cerebrospinal fluid, concomitant pathology, neuropathology, phosphorylated tau, p-tau181, p-tau217, p-tau231
Published in DiRROS: 03.06.2026; Views: 198; Downloads: 162
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Published in DiRROS: 03.06.2026; Views: 168; Downloads: 115
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