Intraneuronal abeta-amyloid precedes development of amyloid plaques in Down syndrome.
BACKGROUND
Down syndrome patients who live to middle age invariably develop the neuropathologic features of Alzheimer disease, providing a unique situation in which to study the early and sequential development of these changes.


OBJECTIVE
To study the development of amyloid deposits, senile plaques, astrocytic and microglial reactions, and neurofibrillary tangles in the brains of young individuals (<30 years of age) with Down syndrome.


METHODS
Histologic and immunocytochemical study of a series of autopsy brains (n = 14, from subjects aged 11 months to 56 years, with 9 subjects <30 years) examined at the Office of the Chief Medical Examiner of the State of Maryland and The Johns Hopkins Hospital.


RESULTS
The principal observations included the presence of intraneuronal Abeta immunostaining in the hippocampus and cerebral cortex of very young Down syndrome patients (preceding the extracellular deposition of Abeta) and the formation of senile plaques and neurofibrillary tangles.


CONCLUSIONS
We propose the following sequence of events in the development of neuropathologic changes of Alzheimer disease in Down syndrome: (1) intracellular accumulation of Abeta in neurons and astrocytes, (2) deposition of extracellular Abeta and formation of diffuse plaques, and (3) development of neuritic plaques and neurofibrillary tangles with activation of microglial cells.
Department of Neuropathy, Armed Forces Institute of Pathology, Washington, DC, USA.
K A
KA
Gyure
R
R
Durham
W F
WF
Stewart
J E
JE
Smialek
J C
JC
Troncoso
D000293:Adolescent; D000328:Adult; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002648:Child; D004314:Down Syndrome / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C419409:amyloid beta-protein (29-40)