Research Brief—Flurizan Fails Final Hurdle, Company Discontinues Drug
Flurizan has floundered in an 18-month Phase 3 clinical trial in patients with mild Alzheimer disease...
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GSAP Revisited: Does It Really Play a Role in Processing Aβ?
A new study finds that the cancer drug imatinib does not lower Aβ in humans, casting doubt on a previously described relationship between imatinib, γ-secretase activating protein (GSAP), and Aβ.
Pathogenic Presenilin Mutations Generate Aβ43
Two new papers rekindle acrimonious debate about exactly what “loss-of-function” means when it comes to presenilin mutations in Alzheimer’s pathogenesis.
Lodged in Late Endosomes, Presenilin 2 Churns Out Intraneuronal Aβ
Presenilin 2 resides almost exclusively in late endosomes, multivesicular bodies, and lysosomes, where it generates a pool of aggregation-prone Aβ. Some PS-1 mutations phenocopy this intraneuronal distribution.
Merck Pulls Plug on Phase 2/3 BACE Inhibitor Trial
The EPOCH trial of verubecestat was halted for lack of efficacy. APECS trial in prodromal AD continues.
Semagacestat, a Pseudo γ-Secretase Inhibitor?
Researchers claim this failed drug allows Aβ to accumulate inside cells, while small peptides cleaved from the C-terminal end of APP become trapped in membranes.
Lymphatic Brain Drain Withers in Aging, Worsens Disease
Aging lymphatic vessels in the meninges hinder waste clearance from the brain and exacerbate Aβ build-up.
Immunotherapy Update: Toward Patches and Creams
In the future, could Alzheimer disease treatments come as an ointment, or a skin patch?...
ApoE Binds Complement Protein, Keeps Inflammatory Cascade in Check
Binding occurs around lipid deposits in the choroid plexus, near Aβ deposits, and also in atherosclerotic plaques in blood vessels.
Does a Breached Blood-Brain Barrier Cause Seizures in AD?
Researchers link age-related weakening of the barrier to TGFβ signaling, hyperexcitation, and cognitive problems. In rodents, TGFβ antagonists attenuate these effects, reducing seizures.
Gaining Notoriety, SORL1 Claims Spot Among Top Alzheimer’s Genes
Recent studies have identified rare loss-of-function variants that cause Alzheimer’s with nearly 100 percent penetrance. Now there are 17 more.
Janus-Faced PLCγ2? Alzheimer’s Risk Protein Toggles TREM2 and TLR Pathways
Acting downstream of TREM2, PLCγ2 facilitates phagocytic microglial behavior such as lipid processing. PLCγ2 also acts downstream of toll-like receptors, where it can throw a switch to inflammation.
Tau: Why Alzheimer’s Worsens Fast in Some, Slowly in Others
A postmortem study found that people who had more aggregation-prone, hyperphosphorylated, oligomeric forms of tau in their brains also had a more aggressive form of Alzheimer’s disease during life. Will we personalize tauopathy care like cancer care?
Does a Stimulating Childhood Stem Amyloid Plaques in Golden Years?
Cognitive enrichment in early life correlated with less Alzheimer’s pathology, and slower cognitive decline, in late life.
China Approves Seaweed Sugar as First New Alzheimer’s Drug in 17 Years
GV-971, an oligosaccharide derived from marine kelp, was approved to treat AD in China. Preclinical studies suggest the drug soothes neuroinflammation by balancing the gut microbiome.
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