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Drug Development.

Alzheimers Dement

December 2024

Signant Health, Blue Bell, PA, USA.

Background: In Alzheimer's Disease trials, the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) are commonly utilized as inclusionary criteria at screening. These measures, however, do not always reaffirm inclusionary status at baseline. Score changes between screening and baseline visits may imply potential score inflation at screening leading to inappropriate participant enrollment.

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Background: Immunotherapy of Alzheimer's disease (AD) is a promising approach to reducing the accumulation of beta-amyloid, a critical event in the onset of the disease. Targeting the group II metabotropic glutamate receptors, mGluR2 and mGluR3, could be important in controlling Aβ production, although their respective contribution remains unclear due to the lack of selective tools.

Method: 5xFAD mice were chronically treated by a brain penetrant camelid single domain antibody (VHH or nanobody) that is an activator of mGluR2.

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Background: Vaxxinity is developing an active immunotherapy targeting Tau for Alzheimer's disease (AD) and other tauopathies. VXX-301 is a multi-epitope vaccine designed to target the N-terminal and repeat domains of Tau. This design enables targeting multiple forms of Tau thought to contribute to Tau associated pathologies.

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Drug Development.

Alzheimers Dement

December 2024

ADEL Institute of Science & Technology (AIST), ADEL, Inc., Seoul, Korea, Republic of (South).

Background: The Apolipoprotein E4 isoform (ApoE4), encoded by the APOE gene, stands out as the most influential genetic factor in late-onset Alzheimer's disease (LOAD). The ApoE4 isoform contributes to metabolic and neuropathological abnormalities during brain aging, with a strong correlation observed in APOE4-positive Alzheimer's disease cases between phosphorylated tau burden and amyloid deposition. Despite compelling evidence of APOE-mediated neuroinflammation influencing the progression of tau-mediated neurodegeneration, the molecular mechanisms underlying these phenomena remain largely unknown.

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Drug Development.

Alzheimers Dement

December 2024

Loma Linda University Health, Loma Linda, CA, USA.

Background: Only about 50% of the variance in cognitive decline occurring during Alzheimer's pathogenesis is attributable to standard AD biomarkers (cerebrocortical Aβ, pathological tau, and atrophy) (Tosun et al., Alzheimer's Dement. 18: 1370, 2022).

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