The Role of Tau beyond Alzheimer’s Disease: A Narrative Review

Virgilio, Eleonora; Marchi, Fabiola De; Contaldi, Elena; Dianzani, Umberto; Cantello, Roberto; Mazzini, Letizia; Comi, Cristoforo

doi:10.3390/biomedicines10040760

Cited by 23 publications

(21 citation statements)

References 168 publications

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“…Based on these premises, there is a demand for robust prognostic markers in early disease phases to identify patients with a higher risk for disease progression and development of CI [ 16 ]. Those markers may help define a future tailored treatment.…”

Section: Introductionmentioning

confidence: 99%

Early Predictors of Disability and Cognition in Multiple Sclerosis Patients: A Long-Term Retrospective Analysis

Virgilio

Vecchio

Sarnelli

et al. 2023

JCM

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We conducted a retrospective analysis on multiple sclerosis (MS) patients with perceived cognitive decline and long disease duration to investigate early predictors of future cognitive impairment (CI) and motor disability. Sixty-five patients complaining of cognitive decline were assessed with an extensive neuropsychological battery at the last clinical follow-up and classified as mildly impaired, severely impaired, and cognitively spared based on the results. Motor disability was assessed with EDSS, MSSS, and ARMSS. Baseline demographic, clinical, and imaging parameters were retrospectively collected and inserted in separate multivariate regression models to investigate the predictive power of future impairment. Twenty-one patients (32.3%) showed no CI, seventeen (26.2%) showed mild CI, and twenty-seven (41.5%) showed severe CI. Older and less educated patients with higher EDSS, longer disease duration, and higher white matter lesion load (WMLL) at diagnosis (particularly with cerebellar involvement) were more likely to develop CI after a mean follow-up from diagnosis of 16.5 ± 6.9 years. DMT exposure was protective. The multivariate regression analyses confirmed WMLL, disease duration, and educational levels as the parameters with significant predictive value for future CI (R2 adjusted: 0.338 p: 0.001). Older patients with progressive phenotype both at diagnosis and T1 were more likely to be not fully ambulatory at T1 (R2 adjusted: 0.796 p: 0.0001). Our results further expand knowledge on early predictors of cognitive decline and evolution over time.

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Section: Introductionmentioning

confidence: 99%

Early Predictors of Disability and Cognition in Multiple Sclerosis Patients: A Long-Term Retrospective Analysis

Virgilio

Vecchio

Sarnelli

et al. 2023

JCM

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“…Lastly, one must bear in mind that similar pathologies may determine different clinical phenotypes, and the same clinical manifestation can be due to different pathological aggregates. As an example, both 3R and 4R tau isoforms are present in FTD and Alzheimer’s disease dementia in straight filaments and paired helical filaments, but involving different vulnerable brain regions and reflecting different phenotypes [ 126 , 127 ].…”

Section: Discussionmentioning

confidence: 99%

The Need for Biomarkers in the ALS–FTD Spectrum: A Clinical Point of View on the Role of Proteomics

Mele¹,

Tondo

Giorgis

et al. 2023

Proteomes

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Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are severely debilitating and progressive neurodegenerative disorders. A distinctive pathological feature of several neurodegenerative diseases, including ALS and FTD, is the deposition of aberrant protein inclusions in neuronal cells, which leads to cellular dysfunction and neuronal damage and loss. Despite this, to date, the biological process behind developing these protein inclusions must be better clarified, making the development of disease-modifying treatment impossible until this is done. Proteomics is a powerful tool to characterize the expression, structure, functions, interactions, and modifications of proteins of tissue and biological fluid, including plasma, serum, and cerebrospinal fluid. This protein-profiling characterization aims to identify disease-specific protein alteration or specific pathology-based mechanisms which may be used as markers of these conditions. Our narrative review aims to highlight the need for biomarkers and the potential use of proteomics in clinical practice for ALS–FTD spectrum disorders, considering the emerging rationale in proteomics for new drug development. Certainly, new data will emerge in the near future in this regard and support clinicians in the development of personalized medicine.

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“…There is an urgent need for noninvasive, reliable fluid biomarkers to diagnose early TDP-43 pathology to improve the differential diagnosis with overlapping neurodegenerative diseases that undoubtedly exhibit an extreme variability in clinical phenotypes, as described by Virgilio et al, for tau [ 112 ]. Since TDP-43 pathology increases linearly with age in older adults with and without dementia [ 113 ], the issue of prevention at early ages is certainly crucial.…”

Section: Discussionmentioning

confidence: 99%

TDP-43 CSF Concentrations Increase Exponentially with Age in Metropolitan Mexico City Young Urbanites Highly Exposed to PM2.5 and Ultrafine Particles and Historically Showing Alzheimer and Parkinson’s Hallmarks. Brain TDP-43 Pathology in MMC Residents Is Associated with High Cisternal CSF TDP-43 Concentrations

Calderón‐Garcidueñas

Stommel

Lachmann³

et al. 2022

Toxics

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Environmental exposures to fine particulate matter (PM2.5) and ultrafine particle matter (UFPM) are associated with overlapping Alzheimer’s, Parkinson’s and TAR DNA-binding protein 43 (TDP-43) hallmark protein pathologies in young Metropolitan Mexico City (MMC) urbanites. We measured CSF concentrations of TDP-43 in 194 urban residents, including 92 MMC children aged 10.2 ± 4.7 y exposed to PM2.5 levels above the USEPA annual standard and to high UFPM and 26 low pollution controls (11.5 ± 4.4 y); 43 MMC adults (42.3 ± 15.9 y) and 14 low pollution adult controls (33.1 ± 12.0 y); and 19 amyotrophic lateral sclerosis (ALS) patients (52.4 ± 14.1 y). TDP-43 neuropathology and cisternal CSF data from 20 subjects—15 MMC (41.1 ± 18.9 y) and 5 low pollution controls (46 ± 16.01 y)—were included. CSF TDP-43 exponentially increased with age (p < 0.0001) and it was higher for MMC residents. TDP-43 cisternal CSF levels of 572 ± 208 pg/mL in 6/15 MMC autopsy cases forecasted TDP-43 in the olfactory bulb, medulla and pons, reticular formation and motor nuclei neurons. A 16 y old with TDP-43 cisternal levels of 1030 pg/mL exhibited TDP-43 pathology and all 15 MMC autopsy cases exhibited AD and PD hallmarks. Overlapping TDP-43, AD and PD pathologies start in childhood in urbanites with high exposures to PM2.5 and UFPM. Early, sustained exposures to PM air pollution represent a high risk for developing brains and MMC UFPM emissions sources ought to be clearly identified, regulated, monitored and controlled. Prevention of deadly neurologic diseases associated with air pollution ought to be a public health priority and preventive medicine is key.

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The Role of Tau beyond Alzheimer’s Disease: A Narrative Review

Cited by 23 publications

References 168 publications

Early Predictors of Disability and Cognition in Multiple Sclerosis Patients: A Long-Term Retrospective Analysis

Early Predictors of Disability and Cognition in Multiple Sclerosis Patients: A Long-Term Retrospective Analysis

The Need for Biomarkers in the ALS–FTD Spectrum: A Clinical Point of View on the Role of Proteomics

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