Abstract
Synaptic dysfunction or loss in early stages of Alzheimer’s disease (AD) is thought to be a major structural correlate of cognitive dysfunction. Early loss of episodic memory, which occurs at the early stage of AD, is closely associated with the progressive degeneration of medial temporal lobe (MTL) structures of which the transentorhinal cortex (TEC) is the first affected area. However, no ultrastructural studies have been performed in this region in human brain samples from AD patients.In the present study, we have performed a detailed three-dimensional (3D) ultrastructural analysis using focused ion beam/scanning electron microscopy (FIB/SEM) to investigate possible synaptic alterations in the TEC of patients with AD. Surprisingly, the analysis of the density, morphological features and spatial distribution of synapses in the neuropil showed no significant differences between AD and control samples. However, light microscopy studies showed that cortical thickness of the TEC was severely reduced in AD samples, but there were no changes in the volume occupied by neuronal and glial cell bodies, blood vessels, and neuropil. Thus, the present results indicate that there is a dramatic loss of absolute number of synapses, while the morphology of synaptic junctions and synaptic spatial distribution are maintained. How these changes affect cognitive impairment in AD remains to be elucidated.
Highlights
Alzheimer’s Disease (AD) is the main cause of dementia, accounting for 60−80% of cases in the adult population [3]
In Nissl-stained sections and sections immunostained for anti-NeuN, the transentorhinal cortex (TEC) was distinguished because layers III and V merge and sweep obliquely to invade layer II of the entorhinal cortex (EC) [10, 14, 24, 85]
In summary, the present results provide support for neuronal and synaptic loss occurring in the TEC, in line with previous studies
Summary
Alzheimer’s Disease (AD) is the main cause of dementia, accounting for 60−80% of cases in the adult population [3]. The disease is characterized by a progressive and persistent decline of cognitive functions, such as memory and orientation. AD is characterized by two hallmark lesions: extracellular amyloid plaques, primarily consisting of amyloid-β (Aβ) peptide, and intracellular neurofibrillary tangles, which consist of filamentous aggregates of hyperphosphorylated tau protein. In addition to these main hallmarks of AD, other neuropathological changes —such as neuronal and synaptic loss— have been described [58]. Synaptic loss seems to be the major structural correlate
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