Clinical and diagnostic implications of Alzheimer’s disease copathology in Lewy body disease DOI
Lorenzo Barba, Samir Abu‐Rumeileh, Henryk Barthel

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(10), P. 3325 - 3343

Published: July 11, 2024

Concomitant Alzheimer's disease (AD) pathology is a frequent event in the context of Lewy body (LBD), occurring approximately half all cases. Evidence shows that LBD patients with AD copathology show an accelerated course, greater risk cognitive decline and overall poorer prognosis. However, LBD-AD cases may heterogeneous motor non-motor phenotypes higher dementia and, consequently, be not rarely misdiagnosed. In this review, we summarize current understanding by discussing synergistic effects neuropathological changes their clinical relevance. Furthermore, provide extensive overview neuroimaging fluid biomarkers under assessment for use possible diagnostic prognostic values. can predicted vivo means CSF, MRI PET markers, whereas most promising technique to date identifying different biological tissues α-synuclein seed amplification assay. Pathological imaging CSF are associated likelihood but do always mirror severity as pure AD. Implementing blood-based might allow faster screening copathology, thus improving sensitivity LBD-AD. Finally, discuss literature on novel candidate being exploited investigate other aspects neurodegeneration, such neuroaxonal injury, glial activation synaptic dysfunction. The thorough characterization should taken into account when considering differential diagnoses syndromes, evaluation individual level, guide symptomatic disease-modifying therapies.

Language: Английский

Cellular and pathological functions of tau DOI
C Bravo, Sarah Naguib, Li Gan

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(11), P. 845 - 864

Published: July 16, 2024

Language: Английский

Citations

34
The neuropathobiology of multiple sclerosis DOI
Marcel S. Woo, Jan Broder Engler, Manuel A. Friese

et al.

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(7), P. 493 - 513

Published: May 24, 2024

Language: Английский

Citations

29
The Importance of Complement-Mediated Immune Signaling in Alzheimer’s Disease Pathogenesis DOI Open Access

André F. Batista,

Khyrul Khan,

Maria-Tzousi Papavergi

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 817 - 817

Published: Jan. 9, 2024

As an essential component of our innate immune system, the complement system is responsible for defense against pathogens. The cascade has complex roles in central nervous (CNS), most what we know about it stems from its role brain development. However, recent years, numerous reports have implicated classical both development and decline. More specifically, dysfunction been neurodegenerative disorders, such as Alzheimer's disease (AD), which common form dementia. Synapse loss one main pathological hallmarks AD correlates with memory impairment. Throughout course progression, synapses are tagged proteins consequently removed by microglia that express receptors. Notably, astrocytes also capable secreting signals induce expression CNS. Both neuroinflammation, another hallmark pathogenesis. In this review, provide overview previously known newly established CNS explore how interactions microglia, astrocytes, other risk factors TREM2 ApoE4 modulate processes neurodegeneration amyloid tau models AD.

Language: Английский

Citations

24
NRF2 Deficiency Promotes Ferroptosis of Astrocytes Mediated by Oxidative Stress in Alzheimer’s Disease DOI
Zhi Tang,

Zhuyi Chen,

Min Guo

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 7517 - 7533

Published: Feb. 24, 2024

Language: Английский

Citations

23
Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles DOI Creative Commons
Pascual Sánchez-Juan, Elizabeth Valeriano-Lorenzo,

Alicia Ruiz-González

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(5), P. 1667 - 1679

Published: Feb. 1, 2024

Glial fibrillary acidic protein (GFAP), a proxy of astrocyte reactivity, has been proposed as biomarker Alzheimer's disease. However, there is limited information about the correlation between blood biomarkers and post-mortem neuropathology. In single-centre prospective clinicopathological cohort 139 dementia patients, for which time-frame GFAP level determination neuropathological assessment was exceptionally short (on average days), we analysed this biomarker, measured at three time points, in relation to proxies disease progression such cognitive decline brain weight. Most importantly, investigated use detect hallmarks disease, while accounting potential influences most frequent co-pathologies. The main findings demonstrated an association serum tau pathology (β = 12.85; P < 0.001) that independent amyloid deposits 13.23; 0.02). A mediation analysis provided additional support role astrocytic activation link Furthermore, negative observed pre-mortem weight (r -0.35; 0.001). This finding, together with evidence assessments -0.27; 0.005), supports monitoring, even late phases Moreover, diagnostic performance advanced patients explored, its discriminative power (area under receiver operator characteristic curve baseline 0.91) differentiating neuropathologically-confirmed dementias from non-Alzheimer's determined, despite challenging scenario age co-pathologies these patients. Independently levels were shown be associated two other pathologies targeting temporal lobes-hippocampal sclerosis 3.64; 0.03) argyrophilic grain -6.11; Finally, revealed correlated using GFAP-immunostained area (ρ 0.21; Our results contribute increasing suggesting offer mechanistic insights into relationship neuropathology, highlighting ties burden. data lesions provide clinicians consider when interpreting test results. longitudinal design reinforce robustness our findings. studies correlating are still scant, further research needed replicate validate diverse populations.

Language: Английский

Citations

23
Inflammatory aspects of Alzheimer’s disease DOI
Pablo Botella Lucena, Michael T. Heneka

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 148(1)

Published: Aug. 28, 2024

Language: Английский

Citations

23
Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank DOI Creative Commons
Xiaofei Wang, Ziyan Shi, Yuhan Qiu

et al.

BMC Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 13, 2024

Peripheral glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are sensitive markers of neuroinflammation neuronal damage. Previous studies with highly selected participants have shown that peripheral GFAP NfL levels elevated in the pre-clinical phase Alzheimer's disease (AD) dementia. However, predictive value for dementia requires more evidence from population-based cohorts.

Language: Английский

Citations

21
The duality of amyloid-β: its role in normal and Alzheimer’s disease states DOI Creative Commons
Ali Azargoonjahromi

Molecular Brain, Journal Year: 2024, Volume and Issue: 17(1)

Published: July 17, 2024

Abstract Alzheimer’s disease (AD) is a degenerative neurological condition that gradually impairs cognitive abilities, disrupts memory retention, and impedes daily functioning by impacting the cells of brain. A key characteristic AD accumulation amyloid-beta (Aβ) plaques, which play pivotal roles in progression. These plaques initiate cascade events including neuroinflammation, synaptic dysfunction, tau pathology, oxidative stress, impaired protein clearance, mitochondrial disrupted calcium homeostasis. Aβ also closely associated with other hallmark features AD, underscoring its significance. generated through cleavage amyloid precursor (APP) plays dual role depending on processing pathway. The non-amyloidogenic pathway reduces production has neuroprotective anti-inflammatory effects, whereas amyloidogenic leads to peptides, Aβ40 Aβ42, contribute neurodegeneration toxic effects AD. Understanding multifaceted Aβ, particularly crucial for developing effective therapeutic strategies target metabolism, aggregation, clearance aim mitigating detrimental consequences disease. This review aims explore mechanisms functions under normal abnormal conditions, examining both beneficial effects.

Language: Английский

Citations

18
Alzheimer blood biomarkers: practical guidelines for study design, sample collection, processing, biobanking, measurement and result reporting DOI Creative Commons
Xuemei Zeng,

Yijun Chen,

Anuradha Sehrawat

et al.

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: May 15, 2024

Abstract Alzheimer’s disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades research clinical investigation. This might be partly due a lack widely available cost-effective modalities for diagnosis prognosis. Recently, blood-based AD biomarker field has seen significant progress driven by technological advances, mainly improved analytical sensitivity precision assays measurement platforms. Several biomarkers have shown high potential accurately detecting pathophysiology. As result, there been considerable interest in applying these prognosis, as surrogate metrics investigate impact various covariates on pathophysiology accelerate therapeutic trials monitor treatment effects. However, standardization how blood samples collected, processed, stored analyzed reported can affect reproducibility measurements, potentially hindering toward their widespread use settings. To help address issues, we provide fundamental guidelines developed according recent findings sample handling measurements. These cover important considerations including study design, collection, processing, biobanking, measurement, result reporting. Furthermore, proposed include best practices appropriate procedures genetic ribonucleic acid analyses. While focus key AT(N) criteria (e.g., amyloid-beta [Aβ]40, Aβ42, Aβ42/40 ratio, total-tau, phosphorylated-tau, neurofilament light chain, brain-derived tau glial fibrillary acidic protein), anticipate that will generally applicable other types biomarkers. We also assist investigators planning executing research, enabling harmonization improve comparability across studies.

Language: Английский

Citations

17
evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer’s disease DOI Creative Commons
Jeffrey L. Cummings, Alireza Atri, Howard Feldman

et al.

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 8, 2025

Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for treatment type 2 diabetes obesity has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms neuroinflammatory, vascular, other AD-related processes. Large randomized controlled trials are needed to assess efficacy early-stage symptomatic AD. evoke evoke+ randomized, double-blind, placebo-controlled phase 3 investigating efficacy, safety, tolerability once-daily oral versus placebo Eligible participants were men or women aged 55–85 years with mild cognitive impairment dementia due confirmed amyloid abnormalities (assessed by positron emission tomography cerebrospinal fluid [CSF] analysis). After maximum 12-week screening phase, anticipated 1840 patients each trial (1:1) 156 weeks (104-week main 52-week extension). Randomized follow 8-week dose escalation regimen (3 mg [weeks 0–4], 7 4–8], 14 8–156]). primary endpoint semaglutide–placebo difference on change from baseline week 104 Clinical Dementia Rating – Sum Boxes score. Analyses plasma biomarkers, collected all participants, CSF sub-study (planned n = 210) will explore effects biomarkers neuroinflammation. Enrollment was undertaken between May 18, 2021, September 8, 2023. Completion trials' expected 2025, extension (in which investigators remain blinded assignment) continue October 2026. first large-scale investigate disease-modifying potential AD, exploration provide data be evaluating its utility Clinicaltrials.gov, NCT04777396 NCT04777409. Date: 02/03/2021

Language: Английский

Citations

6