Resistance to Alzheimer's pathology is associated with nuclear hypertrophy in neurons.
This study focuses on the morphometric changes of neurons in asymptomatic Alzheimer's 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 Abeta or Tau, or a compensatory mechanism which forestalls the progression of AD and allows the brain to resist the development of dementia.
Riudavets
Miguel Angel
MA
Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Iacono
Diego
D
Resnick
Susan M
SM
O'Brien
Richard
R
Zonderman
Alan B
AB
Martin
Lee J
LJ
Rudow
Gay
G
Pletnikova
Olga
O
Troncoso
Juan C
JC
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D002467:Cell Nucleus / Q000473:pathology*; D053145:Cell Nucleus Size / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D003704:Dementia / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D006179:Gyrus Cinguli / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006984:Hypertrophy / Q000209:etiology*; D007113:Immunity, Innate / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology*; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins