👤 Bengt Winblad

Olfactory impairment is common in older age and is a known early feature of several dementia diseases. Blood-based biomarkers of Alzheimer's disease (AD) now offer a scalable method for detecting pathophysiological mechanisms related to olfactory decline in the general population. However, few studies have examined how these biomarkers relate to long-term olfactory trajectories. Most existing work has been limited to cross-sectional settings. In this population-based study, we used biomarker data collected at baseline and followed participants for up to 15 years, enabling us to test whether early biological changes are temporally linked to subsequent olfactory decline. Data came from the ongoing Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a longitudinal population-based study with baseline assessments from March 21, 2001, through August 30, 2004. We included participants without prevalent neurodegenerative diseases who completed olfactory assessment at baseline. The 15-year follow-up was finished in December 2019. Data were analysed from December 2023 to April 2024. Serum-derived biomarkers of tau phosphorylated at threonine 217 (p-tau217) and at theorine181 (p-tau181), total tau (t-tau), amyloid-β ratio (Aβ42/Aβ40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were obtained at baseline. Linear mixed models examined associations between biomarker quartiles and Sniffin' Sticks odor identification performance over 15 years, adjusting for demographics, health conditions, and semantic knowledge. We included 1868 participants (mean [SD] age 71.3 [9.9] years; 1122 females [60.1%]). In fully adjusted models, higher quartiles of p-tau217, p-tau181, NfL, and GFAP, and lower quartiles of Aβ42/Aβ40, were associated with steeper olfactory decline, with the steepest decline among participants in the highest quartiles (β for Q4 vs Q1: -0.20 [95% CI: -0.26 to -0.15] for p-tau217; -0.19 [95% CI: -0.25 to -0.13] for p-tau181; -0.23 [95% CI: -0.29 to -0.17] for NfL; β = -0.17 [95% CI: -0.23 to -0.11] for GFAP. Participants in the lowest Aβ42/Aβ40 quartile declined more steeply than those in the highest (β = -0.09 [95% CI: -0.14 to -0.04]). Associations appeared stronger in the oldest participants, in APOE ε4 carriers for p-tau181, in non-carriers for NfL and GFAP, and among former smokers for NfL. Blood-based biomarkers of AD were consistently associated with faster olfactory decline in older adults, particularly in the highest biomarker quartiles. These results provide large-scale longitudinal evidence, across up to 15 years of follow-up, that olfactory decline in the general population is linked to AD-related blood biomarkers, supporting the hypothesis that common olfactory losses in ageing partly reflect dementia-related processes. Show less

Cerebrospinal fluid (CSF) β-site amyloid precursor protein cleaving enzyme 1 (BACE1), neurogranin and the neurogranin/BACE1 ratio are proposed markers for Alzheimer's disease. BACE1 is also a drug target. However, CSF levels may differ between early-stage amyloid plaque formation (A) and later stage downstream tau-tangle pathology (T) and neurodegeneration (N) and may be expressed as an A/T/N stage (e.g. A+/T-/N or A+/T+/N+). Whether BACE1 and neurogranin levels are persistent traits or change with disease progression is unknown. The aim of this study was to investigate whether CSF neurogranin and BACE1 concentrations differ between A/T/N stages, whether these change over time and correlate with memory decline. This may have implications for patient selection in future trials. We used CSF markers to determine A/T/N stage using amyloid beta42/40 ratio, p-tau181 and total-tau respectively in predementia Alzheimer's disease cases ( Show less

Increased protein level in the cerebrospinal fluid (CSF) is a characteristic of patients with Guillain-Barré syndrome (GBS), an acute inflammatory autoimmune disorder in the peripheral nervous system (PNS). However, the molecular mechanisms underlying the disease remain poorly understood and so far no reliable disease-related markers are available. By comparing the CSF proteome of GBS patients with control subjects suffering from other neurological disorders, it may be possible to identify proteins that involve in the disease process and thus to study the pathogenesis of GBS. We used two-dimensional difference gel electrophoresis (2D DIGE) technique, in combination with matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), to determine the abnormal CSF proteins in GBS patients. Our data showed that the levels of six proteins and their isoforms in CSF were significantly altered in GBS patients compared with controls. Haptoglobin, apolipoprotein A-IV and PRO2044 (unnamed protein) were considerably increased in the CSF of GBS patients, whereas transthyretin, apolipoprotein E and fibrinogen were considerably decreased. We concluded that these six proteins may be involved in the pathogenesis of GBS and call for further studying the role of these proteins in the pathogenesis of the disease. Show less