The path forward in Alzheimer's disease therapeutics: Reevaluating the amyloid cascade hypothesis.

The path forward in Alzheimer's disease therapeutics: Reevaluating the amyloid cascade hypothesis. Alzheimers Dement. 2019 Nov 04;: Authors: Tolar M, Abushakra S, Sabbagh M Abstract Development of disease-modifying treatments for Alzheimer's disease (AD) has been challenging, with no drugs approved to date. The failures of several amyloid-targeted programs have led many to dismiss the amyloid beta (Aβ) hypothesis of AD. An antiamyloid antibody aducanumab recently showed modest but significant efficacy in a phase 3 trial, providing important validation of amyloid as a therapeutic target. However, the inconsistent results observed with aducanumab may be explained by the limited brain penetration and lack of selectivity for the soluble Aβ oligomers, which are implicated as upstream drivers of neurodegeneration by multiple studies. Development of agents that can effectively inhibit Aβ oligomer formation or block their toxicity is therefore warranted. An ideal drug would cross the blood-brain barrier efficiently and achieve sustained brain levels that can continuously prevent oligomer formation or inhibit their toxicity. A late-stage candidate with these attributes is ALZ-801, an oral drug with a favorable safety profile and high brain penetration that can robustly inhibit Aβ oligomer formation. An upcoming phase 3 trial with ALZ-801 in APOE4/4 homozygous patients with early AD will effectively test this amyloid oligomer hypothesis. PMI...
Source: The Journal of Alzheimers Association - Category: Psychiatry Tags: Alzheimers Dement Source Type: research

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Condition:   Alzheimer's Disease Interventions:   Drug: Tricaprilin;   Drug: Placebo Sponsor:   Cerecin Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Publication date: Available online 4 December 2019Source: The Lancet NeurologyAuthor(s): Lon Schneider
Source: The Lancet Neurology - Category: Neurology Source Type: research
Biogen Inc, looking to win over skeptics and health regulators, later on Thursday will present highly anticipated data on its experimental Alzheimer's drug aducanumab, which the U.S. biotech company had declared a failure earlier this year.
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
A study found that the drug that curbs delusions in Parkinson's patients did the same for people with Alzheimer's and other forms of dementia
Source: ABC News: Health - Category: Consumer Health News Tags: Health Source Type: news
In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72.MethodsIn this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death,...
Source: The Lancet Neurology - Category: Neurology Source Type: research
DISCUSSION: The preclinical duration of cognitive and behavioral changes approaches the earliest reported biomarker changes. PMID: 31787561 [PubMed - as supplied by publisher]
Source: The Journal of Alzheimers Association - Category: Psychiatry Tags: Alzheimers Dement Source Type: research
This study compared different methods for collecting data on falls among people with dementia to identify which is most feasible and accurate. Eighty-three dyads, comprised of a community-dwelling person with dementia and their informal carer, participated in the TAi ChI for people with demenTia (TACIT) trial. Falls were collected prospectively over 6 months using monthly calendars, weekly and monthly telephone interviews, and 3-monthly telephone interviews with the carer. Unique falls identified across the reporting methods were combined, and this total was compared against each reporting method in isolation and combinati...
Source: Alzheimer Disease and Associated Disorders - Category: Psychiatry Tags: Alzheimer Dis Assoc Disord Source Type: research
ConclusionsThis is the first study to demonstrate the presence of oligomeric APP-CTFs in AD mouse models, the levels of which are selectively enriched in endolysosomal compartments including exosomes and amplified by γ-secretase inhibition. Future studies should evaluate the putative contribution of these exosome-associated APP-CTFs in AD onset, progression and spreading.
Source: Translational Neurodegeneration - Category: Neurology Source Type: research
Source: MayoClinic.com Full Feed - Category: Consumer Health News Source Type: news
Birth control pills are among the most effective ways to prevent pregnancy, but only if women faithfully take them every day. Human nature being what it is, nearly half of women admit to missing a pill at least once every three months, and, as a result, about 9% of women on oral contraception become pregnant every year. That number would almost certainly fall if women only had to remember to take the pill once a month or so. That’s why researchers at MIT and Brigham and Women’s Hospital (with support from the Gates Foundation) are trying to create a once-a-month birth control pill. In a paper published today (...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized Birth Control embargoed study Reproductive Health Source Type: news
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