Gantenerumab

Blood NfL rises before AD onset but plateaus with symptoms, while CSF NfL continues to accelerate, suggesting CSF NfL may better track neurodegeneration in symptomatic disease.

Research and clinical leaders propose FDA and other agencies to focus approval on amyloid clearance in Alzheimer's disease, based on 40 years of evidence. They suggest setting aside cognitive/clinical change requirements for standard approval of anti-amyloid antibodies that safely remove aggregated Aβ, with downstream biomarker changes indicating disease pathway interference. The proposal aims to accelerate access to disease-modifying treatments.

Long-term cardiovascular drug use linked to fewer dementia diagnoses; anti-platelet use increases risk. Fampridine improves working memory in low-performing adults. MS not a barrier to immune checkpoint inhibitors for cancer. AI identifies Chiari type-1 malformation phenotypes. AI-enabled devices may impact neurology prognoses. ACI-7104.056 induces high anti-alpha-synuclein antibodies in early Parkinson's. Rest tremor correlated with preserved dopamine levels. Hospital care standards proposed for Parkinson's patients. Nerivio migraine treatment device expanded to pediatric use. AI-driven MRI software detects ARIA in Alzheimer's patients. ARIA with edema has no long-term cognitive effect in early Alzheimer's. Systemic dexamethasone improves survival free of cerebral palsy in high-risk bronchopulmonary dysplasia cases. Cancer survivors less likely to develop Alzheimer's. AARP partners to identify dementia risk factors.

Severity of amyloid-beta neuropathology and comorbid cerebrovascular pathology are important baseline risk factors for ARIA-E, in addition to APOE ε4. ARIA-E had no long-term impact on cognitive/functional scale performance in most participants. Clinicians should consider these risk factors when prescribing anti-Aβ monoclonal antibodies for early AD and developing individualized safety monitoring plans.

Trontinemab, a transferrin receptor-based antibody, rapidly removes amyloid plaques with few ARIA cases, but a participant's death from a macrohemorrhage prompts exclusion criteria expansion. Despite safety concerns, CTAD attendees remain optimistic about TfR-based therapies for safer brain delivery.

Despite approvals for Leqembi and Kisunla, attrition in Alzheimer’s and Parkinson’s pipelines persists, with Roche, Johnson & Johnson, Sage Therapeutics, and Otsuka discontinuing programs. Analysts attribute these decisions to clinical trial data and evolving commercial opportunities, noting the Alzheimer’s market is projected to be worth $15.5 billion by 2031, while Parkinson’s drugs are expected to reach $6.63 billion by 2029.

Roche ends Alzheimer’s partnership with UCB, returning rights to Phase 2a candidate bepranemab. This marks Roche's third Alzheimer’s candidate termination this year, following similar actions with AC Immune. Despite setbacks, Roche remains active in early Alzheimer’s diagnosis.

Lecanemab outperformed aducanumab, gantenerumab, and donanemab in binding soluble Aβ aggregates, with donanemab not binding any soluble species, suggesting its efficacy is based solely on plaque clearance. Both lecanemab and aducanumab bound pyroglutamine forms of Aβ, while donanemab did not bind clumped pyroGlu-Aβ, indicating its binding region might be inaccessible in aggregates.

Research highlights the complex roles of tau's post-translational modifications and protease-cleaved fragments in Alzheimer’s Disease and other tauopathies, emphasizing the need for better understanding of target engagement in Tau antibody development and the efficacy of anti-tau antibodies in functional assays.

Alzheimer’s disease (AD) involves progressive neurodegeneration, characterized by cognitive decline and accumulation of β-amyloid protein (Aβ) and neurofibrillary tangles (NFTs). Neuroinflammation, driven by microglia and astrocytes, plays a crucial role in AD pathogenesis. Microglia phagocytose Aβ but can exacerbate disease if overactivated. Astrocytes, though protective, can contribute to neuroinflammation and Aβ production when reactive. Current treatments, including monoclonal antibodies targeting Aβ, show promise but do not reverse disease. Future research aims to mitigate neuroinflammation and enhance protective microglia-astrocyte interactions for potential AD therapies.