The Latest Articles on Biomarkers and Alzheimer's disease
Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles on Biomarkers and Alzheimer's disease
Title: Associations of neuroinflammatory IL-6 and IL-8 with brain atrophy, memory decline, and core AD biomarkers – In cognitively unimpaired older adults
Authors: Elettra Capogna, Leiv Otto Watne, Øystein Sørensen, Carlijn Jamila Guichelaar, Ane Victoria Idland, Nathalie Bodd Halaas, Kaj Blennow, Henrik Zetterberg, Kristine Beate Walhovd, Anders Martin Fjell, Didac Vidal-Piñeiro
Type: Research Article
Abstract:
Concentrations of pro-inflammatory cytokines –interleukin-6 (IL-6) and interleukin-8 (IL-8) – are increased with age and in Alzheimer’s disease (AD). It is not clear whether concentrations of IL-6 and IL-8 in the central nervous system predict later brain and cognitive changes over time nor whether this relationship is mediated by core AD biomarkers. Here, 219 cognitively healthy older adults (62–91 years), with baseline cerebrospinal fluid (CSF) measures of IL-6 and IL-8 were followed over time – up to 9 years – with assessments that included cognitive function, structural magnetic resonance imaging, and CSF measurements of phosphorylated tau (p-tau) and amyloid-β (Aβ-42) concentrations (for a subsample). Higher baseline CSF IL-8 was associated with better memory performance over time in the context of lower levels of CSF p-tau and p-tau/Aβ-42 ratio. Higher CSF IL-6 was related to less CSF p-tau changes over time. The results are in line with the hypothesis suggesting that an up-regulation of IL-6 and IL-8 in the brain may play a neuroprotective role in cognitively healthy older adults with lower load of AD pathology.
Access this article: https://doi.org/10.1016/j.bbi.2023.06.027
Title: Advances in peripheral blood biomarkers of patients with Alzheimer’s disease: Moving closer to personalized therapies
Authors: Gabriella Ferretti, Sara Serafini, Antonella Angiolillo, Paola Monterosso, Alfonso Di Costanzo, Carmela Matrone
Type: Research Article
Abstract:
Recently, measurable peripheral biomarkers in the plasma of ;patients with Alzheimer's disease (AD) have gained considerable clinical interest. Several studies have identified one or more blood signatures that may facilitate the development of novel diagnostic and therapeutic strategies. For instance, changes in peripheral amyloid β42 (Aβ42) levels have been largely investigated in patients with AD and correlated with the progression of the pathology, although with controversial results. In addition, tumor necrosis factor α (TNFα) has been identified as an inflammatory biomarker strongly associated with AD, and several studies have consistently suggested the pharmacological targeting of TNFα to reduce systemic inflammation and prevent neurotoxicity in AD. Moreover, alterations in plasma metabolite levels appear to predict the progression of systemic processes relevant to brain functions. In this study, we analyzed the changes in the levels of Aβ42, TNFα, and plasma metabolites in subjects with AD and compared the results with those in healthy elderly (HE) subjects. Differences in plasma metabolites of patients with AD were analyzed with respect to Aβ42, TNFα, and the Mini-Mental State Examination (MMSE) score, searching for plasma signatures that changed simultaneously. In addition, the phosphorylation levels of the Tyr682 residue of the amyloid precursor protein (APP), which we previously proposed as a biomarker of AD, were measured in five HE and five AD patients, in whom the levels of Aβ42, TNFα, and two plasma lipid metabolites increased simultaneously. Overall, this study highlights the potential of combining different plasma signatures to define specific clinical phenotypes of patient subgroups, thus paving the way for the stratification of patients with AD and development of personalized approaches.
Access this article: https://doi.org/10.1016/j.biopha.2023.115094
Title: Charting the Next Road Map for CSF Biomarkers in Alzheimer’s Disease and Related Dementias
Authors: William T. Hu, Ashima Nayyar & Milota Kaluzova
Type: Review
Abstract:
Clinical prediction of underlying pathologic substrates in people with Alzheimer’s disease (AD) dementia or related dementia syndromes (ADRD) has limited accuracy. Etiologic biomarkers — including cerebrospinal fluid (CSF) levels of AD proteins and cerebral amyloid PET imaging — have greatly modernized disease-modifying clinical trials in AD, but their integration into medical practice has been slow. Beyond core CSF AD biomarkers (including beta-amyloid 1–42, total tau, and tau phosphorylated at threonine 181), novel biomarkers have been interrogated in single- and multi-centered studies with uneven rigor. Here, we review early expectations for ideal AD/ADRD biomarkers, assess these goals’ future applicability, and propose study designs and performance thresholds for meeting these ideals with a focus on CSF biomarkers. We further propose three new characteristics: equity (oversampling of diverse populations in the design and testing of biomarkers), access (reasonable availability to 80% of people at risk for disease, along with pre- and post-biomarker processes), and reliability (thorough evaluation of pre-analytical and analytical factors influencing measurements and performance). Finally, we urge biomarker scientists to balance the desire and evidence for a biomarker to reflect its namesake function, indulge data- as well as theory-driven associations, re-visit the subset of rigorously measured CSF biomarkers in large datasets (such as Alzheimer’s disease neuroimaging initiative), and resist the temptation to favor ease over fail-safe in the development phase. This shift from discovery to application, and from suspended disbelief to cogent ingenuity, should allow the AD/ADRD biomarker field to live up to its billing during the next phase of neurodegenerative disease research.
Access this article: https://doi.org/10.1007/s13311-023-01370-8
Title: Alzheimer's disease biomarkers in cerebrospinal fluid are stable with the Elecsys immunoassay to most pre-analytical influencing factors except freezing at -80°C
Authors: Franz Felix Konen, Hannah Benedictine Maier, Alexandra Neyazi, Stefan Bleich, Konstantin Neumann & Thomas Skripuletz
Type: Research Article
Abstract:
Background:
Alzheimers disease is considered a neurodegenerative disease and is diagnosed by exclusion, while the detection of specific cerebrospinal fluid (CSF) biomarkers, namely amyloid-beta (Abeta) peptides Abeta1-42(ASS42), phospho-tau (181P; P-tau), and total-tau (T-tau), has been shown to improve diagnostic accuracy. Recently, a new generation of sample tubes (Sarstedt false-bottom tubes) for the Elecsys CSF immunoassay for the determination of Alzheimers disease biomarkers in CSF was introduced, promising better measurability. However, the pre-analytic influencing factors have not yet been sufficiently investigated.
Methods:
In 29 patients without Alzheimer's disease diagnosis, CSF concentrations of ASS42, P-tau and T-tau were examined in native CSF and after different influencing interventions using the Elecsys immunoassay test method. The following influencing factors were analyzed: contamination with blood (10,000 and 20,000 erythrocytes/l CSF), 14-day storage at 4°C, blood contamination of CSF and 14-day storage at 4°C, 14-day freezing at -80°C in Sarstedt tubes or glass vials, 3-month intermediate storage at -80°C in glass vials.
Results:
Both storage at -80°C for 14 days in Sarstedt false-bottom tubes and in glass vials and storage at -80°C for 3 months in glass vials resulted in significant decreases in ASS42 (13% after 14 days in Sarstedt and 22% in glass vials, 42% after 3 months in glass vials), P-tau (9% after 14 days in Sarstedt and 13% in glass vials, 12% after 3 months in glass vials) and T-tau (12% after 14 days in Sarstedt and 19% in glass vials, 20% after 3 months in glass vials) concentrations in CSF. No significant differences were found for the other pre-analytical influencing factors.
Conclusion:
Measurements of the concentrations of ASS42, P-tau, and T-tau in CSF with use of the Elecsys immunoassay are robust to the pre-analytical influencing factors of blood contamination and duration of storage. Freezing at -80°C results in significant reduction of biomarker concentrations regardless of the storage tube and must be considered in retrospective analysis.
Access this article: https://doi.org/10.1186/s42466-023-00257-5
Title: Associations of Midlife Lifestyle and Health Factors with Long-Term Changes inBlood-Based Biomarkers of Alzheimer's Disease and Neurodegeneration
Authors: Merten, Natascha; Pinto, A. Alex; Paulsen, Adam J. ;Chen, Yanjun; Engelman, Corinne D.; Hancock, Laura M.; Johnson, Sterling C.; Schubert, Carla R.
Type: Research Article
Abstract:
Background:
Pathological biomarkers of Alzheimer's disease (AD) and other dementias can change decades before clinical symptoms. Lifestyle and health factors might be relevant modifiable risk factors for dementia. Many previous studies have been focusing on associations of lifestyle and health-related factors with clinical outcomes later in life.
Objective:
We aimed to determine to what extent midlife factors of lifestyle, inflammation, vascular, and metabolic health were associated with long-term changes in blood-based biomarkers of AD (amyloid beta (Abeta)) and neurodegeneration (neurofilament light chain (NfL); total tau(TTau)).
Methods:
In 1,529 Beaver Dam Offspring Study (BOSS) participants (mean age 49 years, standard deviation (SD) = 9;54% were women), we applied mixed-effects models with baseline risk factors as determinants and 10-year serum biomarker change as outcomes.
Results:
We found that education and inflammatory markers were associated with levels and/or change over time across all three markers of AD and neurodegeneration in the blood. There were baseline associations of measures of cardiovascular health with lower Abeta42/Abeta40. TTau changed little over time and was higher in individuals with diabetes. Individuals with lower risk in a number of cardiovascular and metabolic risk factors, including diabetes, hypertension, and atherosclerosis had slower accumulation of neurodegeneration over time, as determined by NfL levels.
Conclusion:
Various lifestyle and health factors, including education and inflammation, were associated with longitudinal changes of neurodegenerative and AD biomarker levels in midlife. If confirmed, these findings could have important implications for developing early lifestyle and health interventions that could potentially slow processes of neurodegeneration and AD.
Access this article: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad221287
