Drusen Regression after Macula-involving Rhegmatogenous Retinal Detachment Repair.

Purpose: To investigate the effect of macula-involving rhegmatogenous retinal detachment (RRD) repair on drusen regression.

Methods: A retrospective review was performed of patients with drusen who underwent macula-involving RRD repair. Longitudinal optical coherence tomography scans were reviewed by three graders, and each case was grouped into one of three categories: drusen regression, drusen persistence, or mixed.

Basic Science and Pathogenesis.

Background: Late-onset Alzheimer's disease (LOAD) represents the majority of human AD cases, yet the availability of animal models that accurately reflect LOAD progression and pathology is limited. Traditional transgenic mouse models including 3xTg-AD and 5xFAD rely on supraphysiological overexpression of familial AD risk genes, failing to adequately replicate the disease progression observed in LOAD. Here, we present the first characterization of MODEL-AD1 (MAD1), a platform mouse developed by the Model Organism Development and Evaluation for Late-onset Alzheimer's Disease (MODEL-AD) Consortium.

Basic Science and Pathogenesis.

Background: Genome-Wide Association Studies (GWAS) identified ApoE4 and Trem2*R47H as two of the strongest genetic risk factors for late-onset Alzheimer's Disease (LOAD). As part of our efforts to develop mouse models that better recapitulate LOAD, at Model Organism Development & Evaluation for Late-Onset Alzheimer's Disease (MODEL-AD) consortium at University of California - Irvine, we have created a triple homozygous mouse model that combines our previously developed hAb-KI mice (Jackson Lab #031050), Trem2 (Jackson Lab #034036) and a humanized ApoE4 (Jackson Lab #027894), to evaluate the interactions between aging, hAPOE4, TREM2*R47H, and hAb.

Method: By breeding the hAb-KI, hApoE4 and Trem2, we obtained triple homozygous (HO) mice and we then generated four different groups: WT (C57BL6/J), hAb-KI HO, hAb-KI HO;hApoE4 HO and hAb-KI HO;hApoE4 HO;Trem2 HO.

Basic Science and Pathogenesis.

Background: A case study on a PSEN1 (E280A) carrier with APOECh (R136S) mutation revealed changes in APOE protein function led to a protective effect on AD outcomes. Notably, there is an intriguing disparity between the two hallmark pathologies: a reduction in tauopathy but no change in plaque burden. Given that the APOE protein is predominantly produced by astrocytes and activated microglia, and the APOE gene is among the disease-associated microglia (DAM) genes, it is conceivable that the variance in pathological outcomes may be rooted in the glial response.