Related Experiment Video
Updated: Jun 5, 2026

Quantitative 3D In Silico Modeling (q3DISM) of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
Accelerated amyloid neurodegeneration in HIV-1-infected APP-KI Alzheimer's disease mice
Introduction:
A higher incidence of dementia, including Alzheimer 's-like pathology, is observed in aged people living with HIV-1. However, mechanisms linking HIV-1 to Alzheimer's disease (AD) pathology remain unclear, due to the lack of animal models that allow for concurrent study.
Methods:
We created a novel APP knock-in (KI) AD mouse, NOG/APP KM670,671NL /IL-34 (hNAIL) that permits study of progressive brain HIV-1 replication. The mice harbor human microglia-like cells. Four-month-old CD34+ human cell reconstituted mice infected with the HIV-1 ADA strain facilitated studies of HIV-1 replication on AD pathologies.
Results:
HIV-1 replication increased Aβ levels and reduced synaptic and neuronal integrity. Spatial transcriptomics demonstrated distinct Aβ and HIV-1 transcriptional patterns, whereas dual diseased combinations amplified AD pathology. Neurons showed highest transcriptional change, with genes linked to neuroinflammation, protein trafficking, and synaptic dysfunction.
Discussion:
The hNAIL mice enable interrogation of HIV-AD comorbidities, with a future potential for the development of novel therapeutic interventions.
Related Concept Videos
Alzheimer Disease ll: Pathophysiology
Alzheimer Disease l: Introduction
Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
