Alzheimer\'s disease (AD) is known as the most prevalent type of dementia in the elderly population. However, AD is regarded as a persistent sever clinical challenge due to its high morbidity but low rates of diagnosis and treatment in China. Intracerebral β-Amyloid protein deposition is the earliest pathological process that occurs in the continuous spectrum of AD, prior to clinical symptoms such as cognitive decline. Standardizing the operation and result interpretation of amyloid positron emission tomography (PET) during the clinical practice, and achieving the reliability, repeatability and comparability of the imaging process and results will contribute to the early and accurate diagnosis, efficacy evaluation, and outcome prediction. A global binary interpretation (positive or negative) of amyloid PET images is recommended. In clinical interpretation, amyloid PET image results should be combined with clinical and neuropsychological characteristics, other morphological and/or functional imaging data, and other biological markers.
阿尔茨海默病（AD）是老年期最常见的痴呆类型。患病率高，就诊率、诊断率及治疗率低是长期以来我国AD临床诊疗所面临的严峻挑战。脑内β-淀粉样蛋白沉积是AD连续疾病谱中最早发生的病理过程，先于认知下降等临床症状。规范AD诊疗过程中淀粉样蛋白正电子发射断层显像（PET）的操作和结果判读，实现显像流程及结果的可靠性、可重复性及可比性，将有助于疾病的早期精准诊断、疗效评估、转归预测。推荐对淀粉样蛋白PET图像进行全局二元解读（阳性、阴性）。在临床解读时淀粉样蛋白PET图像结果均应结合临床和神经心理学特征、其他形态和（或）功能性影像资料及其他的生物学标志物。.

Alzheimer\'s disease (AD) is the main cause of dementia, with its diagnosis and management remaining challenging. Amyloid positron emission tomography (PET) has become increasingly important in medical practice for patients with AD. To integrate and update previous guidelines in the field, a task group of experts of several disciplines from multiple countries was assembled, and they revised and approved the content related to the application of amyloid PET in the medical settings of cognitively impaired individuals, focusing on clinical scenarios, patient preparation, administered activities, as well as image acquisition, processing, interpretation and reporting. In addition, expert opinions, practices, and protocols of prominent research institutions performing research on amyloid PET of dementia are integrated. With the increasing availability of amyloid PET imaging, a complete and standard pipeline for the entire examination process is essential for clinical practice. This international consensus and practice guideline will help to promote proper clinical use of amyloid PET imaging in patients with AD.

Primary systemic light chain amyloidosis (SLCA) is characterized by production of light chains that get converted to amyloid fibrils with an affinity for visceral organs and causing organ dysfunction. The therapy for SLCA is directed to recovering the function of the affected organs by targeting the abnormal plasma cell clone and slowing deposition of amyloid fibrils. The NCCN Guidelines for SLCA provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated SLCA.

Attention is being paid to diagnosis and treatment of mild cognitive impairment (MCI) because early diagnosis and preventive management can slow down the progression of Alzheimer\'s disease. In particular, in the present era, the use of biomarkers for predicting conversion into dementia is permitted in medical practice. Therefore, authors aimed to propose additional considerations when updating guidelines for the management of MCI, including predictable biomarkers, revising treatment option after additional clinical trials for cholinesterase inhibitors, and detailed regimes for lifestyle interventions. After reviewing 3 patients with MCI by detailed evaluation, we realized that cholinesterase inhibitors were not recommended. In addition, regular exercise and cognitive training were only possible recommendations for patients according to current guidelines, although all 3 patients had evidence of β-amyloid accumulation and related neurodegeneration. Furthermore, caregivers for all 3 patients were worried whether patients could keep doing regular exercise and cognitive training by themselves and asked about the economic training system which monitors patients so that they can keep training. Therefore, we propose that guidelines for managing MCI need to be updated in the present era when the use of biomarkers for predicting conversion into dementia is permitted in medical practice.

UNASSIGNED: This guideline has been developed jointly by the European Society of Haematology and International Society of Amyloidosis recommending non-transplant chemotherapy treatment for patients with AL amyloidosis.
UNASSIGNED: A review of literature and grading of evidence as well as expert recommendations by the ESH and ISA guideline committees.
UNASSIGNED: The recommendations of this committee suggest that treatment follows the clinical presentation which determines treatment tolerance tempered by potential side effects to select and modify use of drugs in AL amyloidosis. All patients with AL amyloidosis should be considered for clinical trials where available. Daratumumab-VCD is recommended from most untreated patients (VCD or VMDex if daratumumab is unavailable). At relapse, the two guiding principles are the depth and duration of initial response, use of a class of agents not previously exposed as well as the limitation imposed by patients\' fitness/frailty and end organ damage. Targeted agents like venetoclax need urgent prospective evaluation. Future prospective trials should include advanced stage patients to allow for evidence-based treatment decisions. Therapies targeting amyloid fibrils or those reducing the proteotoxicity of amyloidogenic light chains/oligomers are urgently needed.

There was consensus that both amyloid and tau pathologies should be targeted in Alzheimer\'s disease, as well as additional pathophysiological mechanisms such as neuroinflammation. The selection of one or both of these targets may depend upon a personalized approach that takes into account the genetic and acquired factors that cause AD in any given person as well as their stage of disease as reflected in a biomarker profile. The validation of this therapeutic approach will be made possible by new methodologies for subdividing into predominant pathology, by efficient methods for identifying people in the earliest stages of disease, and by combination studies.

To identify the class of evidence for aducanumab use for the treatment of Alzheimer disease and present clinical considerations regarding use.
The author panel systematically reviewed available clinical trial data detailing aducanumab use in individuals with early symptomatic Alzheimer disease. Level of evidence statements were assigned in accordance with the American Academy of Neurology\'s 2017 therapeutic classification of evidence scheme. Safety information, regulatory decisions, and clinical context were also reviewed.
Data were identified from 4 clinical trials, 1 rated Class I and 3 rated Class II. The Class I study showed that single doses of aducanumab up to 30 mg/kg were safe and well tolerated. All 3 Class II studies provided evidence that aducanumab (3-10 mg/kg) decreased amyloid deposition on brain PET at 1 year vs placebo. Efficacy data in the Class II studies varied by dose and outcome, but aducanumab either had no effect on mean change on the Clinical Dementia Rating Sum of Boxes scores or resulted in less worsening (vs placebo) that was of uncertain clinical importance. Adverse amyloid-related imaging abnormalities occurred in approximately 40% of individuals treated with aducanumab vs 10% receiving placebo.
Administration of aducanumab will require expanded clinical infrastructure. Evidence-based guidance is needed to address key questions (e.g., safety in populations not enrolled in phase 3 studies, expected benefits on daily function, treatment duration) and critical issues relating to access to aducanumab (e.g., coverage, costs, burden of monthly infusions) that will inform shared decision making between patients and providers.

Amyloid diseases are caused due to protein homeostasis failure where incorrectly folded proteins/peptides form cross-β-sheet rich amyloid fibrillar structures. Besides proteins/peptides, small metabolite assemblies also exhibit amyloid-like features. These structures are linked to several human and animal diseases. In addition, non-toxic amyloids with diverse physiological roles are characterized as a new functional class. This finding, along with the unique properties of amyloid like stability and mechanical strength, led to a surge in the development of amyloid-based biomaterials. However, the usage of these materials by humans and animals may pose a health risk such as the development of amyloid diseases and toxicity. This is possible because amyloid-based biomaterials and their fragments may assist seeding and cross-seeding mechanisms of amyloid formation in the body. This review summarizes the potential uses of amyloids as biomaterials, the concerns regarding their usage, and a prescribed workflow to initiate a regulatory approach.

Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5-15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer\'s disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI.

The neuropancreatic polypeptide hormone amylin forms pancreatic islet amyloid in type-2 diabetes. Islet amyloid formation contributes to β-cell death in the disease and to the failure of islet transplants, but the features which influence amylin amyloidogenicity are not understood. We constructed an amino acid sequence alignment of 202 sequences of amylin and used the alignment to design consensus sequences of vertebrate amylins, mammalian amylins, and primate amylins. Amylin is highly conserved, but there are differences between human amylin and each consensus sequence, ranging from one to six substitutions. Biophysical analysis shows that all of the consensus sequences form amyloid but do so more slowly than human amylin in vitro. The rate of amyloid formation by the primate consensus sequence is 3- to 4-fold slower than human amylin; the mammalian consensus sequence is approximately 20- to 25-fold slower, and the vertebrate consensus sequence is approximately 6-fold slower. All of the consensus sequences are moderately less toxic than human amylin toward a cultured β-cell line, with the vertebrate consensus sequence displaying the largest reduction in toxicity of 3- to 4-fold. All of the consensus sequences activate a human amylin receptor and exhibit only modest reductions in activity, ranging from 3- to 4-fold as judged by a cAMP production assay. The analysis argues that there is no strong selective evolutionary pressure to avoid the formation of islet amyloid and provides information relevant to the design of less amyloidogenic amylin variants.