Publications by authors named "L Lannfelt"
Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.
J Prev Alzheimers Dis
January 2025
The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.
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- Recent research on immunotherapy for Alzheimer's disease highlights the need to understand how different antibodies bind to amyloid-beta (Aβ), as this affects their effectiveness and potential side effects.
- Lecanemab, a specific IgG1 antibody, was studied using brain samples from Alzheimer's patients and non-demented controls to explore its interactions with various Aβ forms, revealing high levels of insoluble Aβ, especially Aβ42, in Alzheimer's subjects.
- Findings indicate that lecanemab binds primarily to soluble aggregated Aβ protofibrils rather than insoluble Aβ plaques, suggesting a targeted approach in treating Alzheimer's through the modulation of these specific proteins.
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- The study investigated the effects of mAb158, an antibody that targets soluble amyloid beta protofibrils, on aged mice with Alzheimer's-related Aβ pathology.
- Mice treated with mAb158 showed significant reductions in Aβ protofibril levels after 4 weeks and amyloid plaque load after 18 weeks, with effects persisting for 12 weeks post-treatment.
- Upon ending the treatment, levels of Aβ protofibrils and plaques increased again, highlighting the need for ongoing treatment to sustain the benefits on Aβ pathology.
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- Therapeutic antibodies targeting amyloid-beta (Aβ) have been developed to help slow Alzheimer's disease progression, but they can lead to side effects known as amyloid-related imaging abnormalities with edema (ARIA-E).
- This study examined how these antibodies bind to cerebral amyloid angiopathy (CAA) fibrils isolated from human brain tissue to see if there’s a link to the occurrence of ARIA-E in clinical trials.
- Results showed significant differences in binding behavior; some antibodies like solanezumab and crenezumab had minimal binding and no ARIA-E cases, while others like aducanumab and gantenerumab showed high binding and increased ARIA-E frequencies.
Deposition of amyloid beta (Aβ) into plaques is a major hallmark of Alzheimer's disease (AD). Different amyloid precursor protein (APP) mutations cause early-onset AD by altering the production or aggregation properties of Aβ. We recently identified the Uppsala APP mutation (APPUpp), which causes Aβ pathology by a triple mechanism: increased β-secretase and altered α-secretase APP cleavage, leading to increased formation of a unique Aβ conformer that rapidly aggregates and deposits in the brain.
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