Resistance to Alzheimerʹs pathology is associated with nuclear hypertrophy in neurons

This study focuses on the morphometric changes of neurons in asymptomatic Alzheimerʹs disease (AD), a state characterized by the presence of AD lesions in subjects without cognitive impairment. In autopsy brains, we used stereological methods to compare the cell body and nuclear volumes of anterior cingulate gyrus (ACG) and CA1 hippocampal neurons in asymptomatic AD subjects (n = 9), subjects with AD dementia (AD, n = 8), mild cognitive impairment (MCI, n = 9), and age-matched controls (controls, n = 9). In ACG, we observed a significant decrease in the neuronal volume of MCI and AD compared to controls; by contrast, no atrophy was present in asymptomatic AD. Moreover, we found a significant increase in nuclear volume in asymptomatic AD compared to controls (P < 0.001), MCI (P < 0.01) and AD (P < 0.001) brains. Similar results were found in the CA1 region of the hippocampus. This nuclear hypertrophy may represent an early neuronal reaction to Aβ or Tau, or a compensatory mechanism which forestalls the progression of AD and allows the brain to resist the development of dementia.