Related Experiment Video
Updated: Jun 10, 2026

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons
Published on: October 30, 2018
Endogenously generated Dutch-type Aβ non-fibrillar aggregates dysregulate presynaptic neurotransmission in the
Emilie L Castranio1, Merina Varghese2,3,4, Elentina K Argyrousi5
1Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Background:
APPE693Q ("Dutch") transgenic mice develop aging-related learning deficits and accumulate endogenously generated non-fibrillar aggregates (NFAs) of amyloid beta (Aβ) and amyloid precursor protein α-carboxy terminal fragments. NFA-Aβ correlates with synaptic loss and memory deficits more closely than does fibrillar Aβ.
Methods:
We assessed the physiological, transcriptomic, ultrastructural, histological, and metabolic changes associated with the accumulation of NFA of Dutch Aβ in brains of APPE693Q mice.
Results:
Aging-related accumulation of NFA-Aβ in APPE693Q mice was revealed by A11 immunohistochemistry and cyclic D,L-α-peptide-fluorescein-5-isothiocyanate microscopy. Presynaptic termini of APPE693Q mice developed physiological abnormalities in post-tetanic potentiation, synaptic fatigue, synaptic vesicle replenishment, and an aging-related reduction in mitochondrial complex I activity. Single-cell RNA sequencing showed that excitatory neurons exhibited an altered transcriptomic profile involving "protein translation" and "oxidative phosphorylation."
Discussion:
Accumulation of NFA-Aβ alters neuronal metabolism but does not activate inflammation. Depletion of all forms of Aβ may be required to eliminate Aβ toxicity with anti-amyloid antibodies.
Related Concept Videos
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
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...

