Alzheimer disease: Therapeutic strategies Edited by E. Giacobini and R. Becker; Birkhauser; Boston, 1994; xiv + 509 pp. $ 74.50. ISBN 0-8176-3757-5

Unknow

Moving fluid biomarkers for Alzheimer's disease from research tools to routine clinical diagnostics

Four fluid-based biomarkers have been developed into diagnostic tests for Alzheimer’s disease (AD) pathology: the ratio of 42 to 40 amino acid-long amyloid β, a marker of plaque pathology; total-tau and phosphorylated tau, markers of AD-related changes in tau metabolism and secretion; and neurofilament light, a marker of neurodegeneration. When measured in cerebrospinal fluid, these biomarkers can be used in clinical practice to support a diagnosis of mild cognitive impairment or dementia due to AD. Recently, technological breakthroughs have made it possible to measure them in standard blood samples as well. Here, we give an updated account of the current state of the fluid-based AD biomarker research field. We discuss how the new blood tests may be used in research and clinical practice, and what role they may play in relation to more established diagnostic tests, such as CSF biomarkers and amyloid and tau positron emission tomography, to facilitate the effective implementation of future disease-modifying therapies

An update on fluid biomarkers for neurodegenerative diseases: recent success and challenges ahead.

Over the last twenty years, the characterization of Alzheimer's disease (AD) patients has progressed from a description of clinical symptomatology followed by neuropathological findings at autopsy to in vivo pathophysiological signatures using cerebrospinal fluid (CSF) and positron emission tomography (PET). Additionally, CSF biomarkers now reflect synaptic pathology, axonal injury and neuroinflammation. Novel techniques are capable of measuring proteins of pathophysiological importance at femtomolar concentrations in blood (e.g. amyloid, tau species and neurofilaments), which enable screening of large populations in the near future. This will be essential for secondary prevention trials and clinical management. However, common diseases such as dementia with Lewy bodies, Parkinson's disease and frontotemporal dementias, are still without reliable diagnostic biomarkers, although emerging techniques show promising pilot results for some of these diseases. This is likely to change in the next few years, which will be crucial to stratify populations enrolling in clinical trials, since pathologies often coexist

Blood neurofilament light in remote settings: Alternative protocols to support sample collection in challenging pre-analytical conditions

INTRODUCTION: This study investigated alternative pre‐analytical handling of blood for neurofilament light (NfL) analysis where resources are limited. METHOD: Plasma NfL was measured with single molecule array after alternative blood processing procedures: dried plasma spots (DPS), dried blood spots (DBS), and delayed 48‐hour centrifugation. These were compared to standardized plasma processing (reference standard [RS]). In a discovery cohort (n = 10) and a confirmatory cohort (n = 21), whole blood was obtained from individuals with unknown clinical etiology. In the confirmatory cohort, delayed centrifugation protocol was paired with either 37°C incubation or sample shaking to test the effect of these parameters. RESULTS: Delayed centrifugation (R^{2}= 0.991) and DPS (discovery cohort, R^{2} = 0.954; confirmatory cohort, DPS: R^{2} = 0.961) methods were strongly associated with the RS. Delayed centrifugation with higher temperatures (R^{2} = 0.995) and shaking (R^{2} = 0.975) did not affect this association. DPS (P < 0.001) returned concentrations considerably lower than the RS. DISCUSSION: did not affect this association. DPS (P < 0.001) returned concentrations considerably lower than the RS

Refining the amyloid β peptide and oligomer fingerprint ambiguities in Alzheimer’s disease: Mass spectrometric molecular characterization in brain, cerebrospinal fluid, blood, and plasma

Since its discovery, amyloid-β (Aβ) has been the principal target of investigation of in Alzheimer's disease (AD). Over the years however, no clear correlation was found between the Aβ plaque burden and location, and AD associated neurodegeneration and cognitive decline. Instead, diagnostic potential of specific Aβ peptides and/or their ratio, was established. For instance, a selective reduction of the concentration of the aggregation-prone 42 amino acid-long Aβ peptide (Aβ42) in cerebrospinal fluid (CSF) was put forward as reflective of Aβ peptide aggregation in the brain. With time, Aβ oligomers - the proposed toxic Aβ intermediates - have emerged as potential drivers of synaptic dysfunction and neurodegeneration in the disease process. Oligomers are commonly agreed upon to come in different shapes and sizes, and are very poorly characterized when it comes to their composition and their "toxic" properties. The concept of structural polymorphism - a diversity in conformational organization of amyloid aggregates - that depends on the Aβ peptide backbone, makes characterization of Aβ aggregates and their role in AD progression challenging. In this review, we revisit the history of Aβ discovery and initial characterization and highlight the crucial role mass spectrometry (MS) has played in this process. We critically review the common knowledge gaps in the molecular identity of the Aβ peptide, and how MS is aiding characterization of higher order Aβ assemblies. Finally, we go on to presenting recent advances in MS approaches for characterization of Aβ as single peptides and oligomers, and convey our optimism, as to how MS holds a promise for paving the way for progress towards a more comprehensive understanding of Aβ in AD research

Salivary Biomarkers for Alzheimer's Disease and Related Disorders

The search for accessible and cost-effective biomarkers to complement current cerebrospinal fluid (CSF) and imaging biomarkers in the accurate detection of Alzheimer disease (AD) and other common neurodegenerative disorders remains a challenging task. The advances in ultra-sensitive detection methods has highlighted blood biomarkers (e.g. amyloid-β and neurofilament light) as a valuable and realistic tool in a diagnostic or screening process. Saliva, however, is also a rich source of potential biomarkers for disease detection and offers several practical advantages over biofluids that are currently examined for neurodegenerative disorders. However, while this may be true for the general population, challenges in collecting saliva from an elderly population should be seriously considered. In this review, we begin by discussing how saliva is produced and how age-related conditions can modify saliva production and composition. We then focus on the data available which support the concept of salivary amyloid-β, tau species and novel biomarkers in detecting AD and alpha-synuclein (α-syn) in Parkinson’s disease (PD)