Practical recommendations for timely, accurate diagnosis of symptomatic Alzheimer’s disease (MCI and dementia) in primary care: a review and synthesis

Journal of Internal Medicine, Год журнала: 2021, Номер 290(2), С. 310 - 334

Опубликована: Янв. 18, 2021

Abstract The critical role of primary care clinicians (PCCs) in Alzheimer’s disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms disease‐modifying therapies (DMTs) emerge. Our understanding AD has grown substantially: no longer conceptualized a late‐in‐life syndrome cognitive functional impairments, we now recognize that pathology builds silently for decades before impairment is detectable. Clinically, first manifests subtly mild (MCI) due to progressing dementia. Emerging optimism improved outcomes stems from focus on preventive interventions midlife timely, biomarker‐confirmed at early signs deficits (i.e. MCI dementia). A timely particularly important optimizing patient enabling the appropriate use anticipated DMTs. An accelerating challenge PCCs specialists will be respond innovations diagnostics therapy system not currently well positioned do so. To overcome these challenges, collaborate closely navigate optimize dynamically evolving face opportunities. In spirit this collaboration, summarize here some prominent influential models inform our current AD. We also advocate accurate biomarker‐defined) doing so, consider issues related detecting emerging biomarkers clinic.

Язык: Английский

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Time course of phosphorylated-tau181 in blood across the Alzheimer’s disease spectrum

Brain, Год журнала: 2020, Номер 144(1), С. 325 - 339

Опубликована: Окт. 26, 2020

Abstract Tau phosphorylated at threonine 181 (p-tau181) measured in blood plasma has recently been proposed as an accessible, scalable, and highly specific biomarker for Alzheimer’s disease. Longitudinal studies, however, investigating the temporal dynamics of this novel are lacking. It is therefore unclear when disease process p-tau181 increases above physiological levels how it relates to spatiotemporal progression characteristic pathologies. We aimed establish natural time course across sporadic spectrum comparison those established imaging fluid-derived biomarkers examined longitudinal data from a large prospective cohort elderly individuals enrolled Disease Neuroimaging Initiative (ADNI) (n = 1067) covering wide clinical normal cognition dementia, with measures 18F-florbetapir amyloid-β PET scan baseline. A subset participants 864) also had amyloid-β1–42 CSF, another 298) undergone 18F-flortaucipir tau 6 years later. performed brain-wide analyses investigate associations baseline change regional pathology burden later, estimated changes other using previously developed method construction long-term trajectories shorter-term data. Smoothing splines demonstrated that earliest occurred even before markers reached abnormal levels, greater rates correlating increased pathology. Voxel-wise yielded relatively weak, yet significant, early accumulating brain regions cognitively healthy individuals, while strongest were observed late patients mild cognitive impairment. Cross-sectional particularly associated widespread cortical aggregation temporoparietal typical neurofibrillary tangle distribution Finally, we reaches ∼6.5 5.7 after CSF amyloid-β, respectively, following similar p-tau181. Our findings suggest presence aggregation, providing clear implications use diagnostic screening tool

Язык: Английский

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Diagnostic and therapeutic potential of exosomes in Alzheimer’s disease

Journal of Neurochemistry, Год журнала: 2020, Номер 156(2), С. 162 - 181

Опубликована: Июль 3, 2020

Exosomes are small extracellular vesicles released by almost all cell types in physiological and pathological conditions. The exosomal potential to unravel disease mechanisms, or be used as a source of biomarkers, is being explored, particularly the field neurodegenerative diseases. Alzheimer's (AD) most prevalent world exosomes appear have relevant role pathogenesis. This review summarizes current knowledge on exosome contributions AD well their use biomarker resources therapeutic targets. recent findings with respect both protein miRNA candidates for AD, herein described, highlight state art this encourage derived from biofluids clinical practice near future.

Язык: Английский

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Remote Blood Biomarkers of Longitudinal Cognitive Outcomes in a Population Study

Annals of Neurology, Год журнала: 2020, Номер 88(6), С. 1065 - 1076

Опубликована: Авг. 16, 2020

Objective The longitudinal association of the blood biomarkers total tau (t‐tau), neurofilament light (Nf‐L), and glial fibrillary acidic protein (GFAP) with common sporadic Alzheimer disease (AD) cognitive decline is not established. Methods Using a single molecule array technology, ultrasensitive immunoassays for serum concentrations t‐tau, Nf‐L, GFAP were measured in population sample 1,327 participants (60% African Americans women) who had clinical evaluation AD, completed in‐home assessments, undergone 1.5T structural magnetic resonance imaging. Results Higher associated development AD; especially, time‐specific associations notable: t‐tau 8 to 16 years, Nf‐L 4 years prior AD. Serum faster over years; baseline > 0.40pg/ml 30% decline, 25.5pg/ml 110% 232pg/ml 130% compared those lowest quartile. Participants showed 160% hippocampal volume values < 160pg/ml. Additionally, higher was increase 3rd ventricular volume, cortical thickness. Interpretation predict AD changes brain characteristics, suggesting their usefulness only as screening predictive biomarkers, but also capturing pathogenesis dementia. ANN NEUROL 2020;88:1065–1076

Язык: Английский

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Advances and considerations in AD tau-targeted immunotherapy

Neurobiology of Disease, Год журнала: 2019, Номер 134, С. 104707 - 104707

Опубликована: Дек. 10, 2019

The multifactorial and complex nature of Alzheimer's disease (AD) has made it difficult to identify therapeutic targets that are causally involved in the process. However, accumulating evidence from experimental clinical studies investigate early process point towards required role tau AD etiology. Importantly, a large number characterize plethora pathological forms protein onset propagation. Immunotherapy is one most approaches anticipated make difference field therapeutics. Tau -targeted immunotherapy new direction after failure amyloid beta (Aß)-targeted growing highlight Aß-independent It now well established alone will likely be insufficient as monotherapy. Therefore, this review discusses updates on tau-targeted studies, AD-relevant species, promising biomarkers prospect combination therapies surround propagation an efficient timely manner.

Язык: Английский

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Nanomedicine-based technologies and novel biomarkers for the diagnosis and treatment of Alzheimer’s disease: from current to future challenges

Journal of Nanobiotechnology, Год журнала: 2021, Номер 19(1)

Опубликована: Апрель 29, 2021

Abstract Increasing life expectancy has led to an aging population, which consequently increased the prevalence of dementia. Alzheimer's disease (AD), most common form dementia worldwide, is estimated make up 50–80% all cases. AD cases are expected reach 131 million by 2050, and this increasing will critically burden economies health systems in next decades. There currently no treatment that can stop or reverse progression. In addition, late diagnosis constitutes a major obstacle effective management. Therefore, improved diagnostic tools new treatments for urgently needed. review, we investigate describe both well-established recently discovered biomarkers could potentially be used detect at early stages allow monitoring Proteins such as NfL, MMPs, p-tau217, YKL-40, SNAP-25, VCAM-1, Ng / BACE some promising because their successful use tools. explore recent molecular strategies therapeutic approach nanomedicine-based technologies, target drugs brain serve devices tracking progression biomarkers. State-of-the-art nanoparticles, polymeric, lipid, metal-based, being widely investigated potential improve effectiveness conventional novel compounds treating AD. The studies on these nanodevices deeply explained discussed review. Graphic

Язык: Английский

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Transitioning from cerebrospinal fluid to blood tests to facilitate diagnosis and disease monitoring in Alzheimer's disease

Journal of Internal Medicine, Год журнала: 2021, Номер 290(3), С. 583 - 601

Опубликована: Май 22, 2021

Alzheimer's disease (AD) is increasingly prevalent worldwide, and disease-modifying treatments may soon be at hand; hence, now, more than ever, there a need to develop techniques that allow earlier secure diagnosis. Current biomarker-based guidelines for AD diagnosis, which have replaced the historical symptom-based guidelines, rely heavily on neuroimaging cerebrospinal fluid (CSF) sampling. While these greatly improved diagnostic accuracy of pathophysiology, they are less practical application in primary care, population-based epidemiological settings, or where resources limited. In contrast, blood accessible cost-effective source biomarkers AD. this review paper, using recently proposed amyloid, tau neurodegeneration [AT(N)] criteria as framework towards biological definition AD, we discuss recent advances biofluid-based biomarkers, with particular emphasis those potential translated into blood-based biomarkers. We provide an overview research conducted both CSF draw conclusions show promise. Given evidence collated review, plasma neurofilament light chain (N) phosphorylated (p-tau; T) translation clinical practice. However, p-tau requires comparisons between its various epitopes before can made one most robustly differentiates from non-AD dementias. Plasma amyloid beta (A) would prove invaluable early screening modality, but it very precise tests robust pre-analytical protocols.

Язык: Английский

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Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

Biomedicines, Год журнала: 2020, Номер 8(10), С. 421 - 421

Опубликована: Окт. 15, 2020

Neurodegeneration is a highly complex process which associated with variety of molecular mechanisms related to ageing. Among neurodegenerative disorders, Alzheimer’s disease (AD) the most common, affecting more than 45 million individuals. The underlying involve amyloid plaques and neurofibrillary tangles (NFTs) deposition, will subsequently lead oxidative stress, chronic neuroinflammation, neuron dysfunction, neurodegeneration. current diagnosis methods are still limited in regard possibility accurate early detection diseases. Therefore, research has shifted towards identification novel biomarkers matrices as biomarker sources, beyond amyloid-β tau protein levels within cerebrospinal fluid (CSF), that could improve AD diagnosis. In this context, aim paper provide an overview both conventional for found body fluids, including CSF, blood, saliva, urine, tears, olfactory fluids.

Язык: Английский

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Blood biomarkers for the diagnosis of amnestic mild cognitive impairment and Alzheimer’s disease: A systematic review and meta-analysis

Neuroscience & Biobehavioral Reviews, Год журнала: 2021, Номер 128, С. 479 - 486

Опубликована: Июль 7, 2021

Язык: Английский

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Detection of β-amyloid positivity in Alzheimer’s Disease Neuroimaging Initiative participants with demographics, cognition, MRI and plasma biomarkers

Brain Communications, Год журнала: 2021, Номер 3(2)

Опубликована: Фев. 2, 2021

gold standard for the ante-mortem assessment of brain β-amyloid pathology is currently positron emission tomography or cerebrospinal fluid measures

Язык: Английский

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