A quantitative study of abnormally enlarged neurons in cognitively normal brain and neurodegenerative disease

Abnormally enlarged neurons (AEN) occur in many neurodegenerative diseases. To define AEN more objectively, the frequency distribution of the ratio of greatest cell diameter (CD) to greatest nuclear diameter (ND) was studied in populations of cortical neurons in tissue sections of seven cognitively normal brains. The frequency distribution of CD/ND deviated from a normal distribution in 15 out of 18 populations of neurons studied and hence, the 95th percentile (95P) was used to define a limit of the CD/ND ratio excluding the 5% most extreme observations. The 95P of the CD/ND ratio varied from 2.0 to 3.0 in different cases and regions and a value of 95P = 3.0 was chosen to define the limit for normal neurons under non-pathological conditions. Based on the 95P = 3.0 criterion, the proportion of AEN with a CD/ND ≥ 3 varied from 2.6% in Alzheimer's disease (AD) to 20.3% in Pick's disease (PiD). The data suggest: (1) that a CL/ND ≥ 3.0 may be a useful morphological criterion for defining AEN, and (2) AEN were most numerous in PiD and corticobasal degeneration (CBD) and least abundant in AD and in dementia with Lewy bodies (DLB).