A new report paints a stark picture of the coming wave of dementia cases and their staggering cost if prevention or treatment fails to stem the tide.
Scanning for amyloid plaques in the brain may help clinicians diagnose and manage patients with a questionable diagnosis of Alzheimer’s.
The largest trial yet of ApoE4 carriers is pioneering new protocols with increasing use of technology to reach thousands of potential participants and disclose risk information.
Prevention trials are testing new protocols for telling potential participants about their heightened risk for dementia, and exploring the psychological effect of such disclosures.
The intracellular domain of the amyloid precursor protein may alter gene expression to reduce production of Aβ.
The synaptic protein abounds in the cerebrospinal fluid of AD patients and in those in the prodromal phase of the disease.
Researchers have generated the first atomic-level structure of γ-secretase. The new view revealed interactions between amino acid residues and the locations of familial Alzheimer’s disease mutations.
In a clinical trial, people who used the surgically implanted breathing-assist device died nearly a year sooner than those who used only an oxygen mask.
To participate in secondary prevention trials, people must learn that they are at heightened risk for Alzheimer’s disease, either because they are accumulating brain amyloid, or because they carry an ApoE4 allele. How will people handle this knowledge, and how should clinicians communicate it to minimize psychological ill effects? At AAIC, speakers outlined how the A4 trial and Alzheimer Prevention Initiative’s ApoE4 study are going about disclosure, and discussed their challenges. Preliminary data indicate that most trial participants take the news in stride, perhaps paving the way for an era in which AD risk disclosure will become part of standard medical practice. Read Alzforum’s coverage.
Amyloid—check! Neurodegeneration—check! Synaptic integrity … coming soon? The core neuropathologies of Alzheimer’s disease are reflected in cerebrospinal fluid, aiding in the diagnosis and characterization of patients. In contrast, a CSF biomarker of synaptic loss remains elusive. Research presented at this year's AAIC meeting in Washington, D.C., suggests that neurogranin may fit the bill. The synaptic protein creeps up in CSF in the mild cognitive impairment phase of AD, and maybe even before. Brain imaging measures support the idea that CSF neurogranin reflects structural brain changes. Whether it offers a read-out distinct from more-established neurodegeneration markers, such as CSF tau, will likely determine whether neurogranin finds a place in the biomarker toolkit.
Wielding a cryo-electron microscope, researchers have produced the highest-resolution structure of γ-secretase to date. The new structure of the four-subunit machine, which churns out Aβ and other substrates, brings clarity to the complex’s mishmash of 20 transmembrane domains, and suggests how specific amino acid interactions help the promiscuous enzyme snip a striking variety of substrates. A map of Alzheimer’s disease-linked mutations revealed that many line up on intramembrane helices that face the core of the secretase.
Research presented at this year's AAIC meeting in Washington, D.C., lent credence to the idea that the course of brain development in early life influences whether and how dementia manifests later on. Epidemiological, imaging, and genetic studies converged on the idea that learning disabilities linked to particular areas of the cerebral cortex, and portend certain subtypes of Alzheimer's disease. Studying these specific associations may deepen our understanding of dementia in general, scientists say.
A dip in Aβ42 in the cerebrospinal fluid is a handy indicator of amyloid accumulation in the brain. However, efforts to use this marker as a diagnostic have been hampered by measurement variability. At AAIC, researchers presented a possible solution: get rid of the human component and use fully automated systems instead. A handful of these machines are working their way through regulatory approval processes, and one day could serve as quick and accurate tests that spit out results in minutes. How widely the machines will be used, and whether they will ever supplant amyloid PET, will come down to accuracy, price, and payer reimbursement.
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- Wim Annaert on New WAVE in Aβ Production—AICD Tempers APP Processing
- Frédéric Checler on New WAVE in Aβ Production—AICD Tempers APP Processing
- Katalin Scherer on Study Suggests Respiratory Pacemaker Reduces ALS Survival
- Angeliki Nikolakopoulou and Berislav Zlokovic on Could Neutrophils Be the Newest Players in Neurodegenerative Disease?
- John Hardy on γ-Secretase Revealed in Atomic Glory
- Rita Guerreiro and John Hardy on γ-Secretase Revealed in Atomic Glory