Induction of beta (A4)-amyloid in primates by injection of Alzheimer's disease brain homogenate. Comparison with transmission of spongiform encephalopathy.
Amyloid plaques, associated with argyrophilic dystrophic neurites, and cerebral amyloid angiopathy (CAA), but no neurofibrillary tangles, were found in the brains of three middle-aged marmoset monkeys that had been injected intracerebrally (ic) 6-7 yr earlier with brain tissue from a patient with early-onset Alzheimer's disease. Such changes were not found in the brains of three age-matched control marmosets. Immunochemically the amyloid plaques and CAA stained with antibody to beta (A4)-protein. The plaques and CAA displayed dichroic birefringence when stained with Congo red and viewed under polarized light. beta (A4)-amyloid plaques and CAA were also found in the brain of one of two marmosets injected ic 6 yr previously with brain tissue from a patient with prion disease with concomitant beta (A4)-amyloid plaques and CAA. An occasional beta (A4)-amyloid plaque was found in the brains of two of four marmosets injected ic > 4.5 yr previously with brain tissue from three elderly patients, two of whom had suspected (but untransmitted) CJD. No beta (A4)-amyloid plaques or CAA were found in six marmosets who were older than the injected animals, in four marmosets that had not developed spongiform encephalopathy (SE) having been injected several years previously with human brain tissue from three younger patients with suspected or atypical prion disease, or in 10 younger marmosets who had undergone various neurosurgical procedures. Seventeen marmosets injected in the same way with brain tissue from patients or animals with SE developed SE 17-49 mo after injection. These results suggest that beta (A4)-amyloidosis is a transmissible process comparable to the transmissibility of SE.
Baker
H F
HF
Clinical Research Centre, Harrow, Middlesex, UK.
Ridley
R M
RM
Duchen
L W
LW
Crow
T J
TJ
Bruton
C J
CJ
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D002144:Callithrix / Q000378:metabolism*; D016657:Cerebral Amyloid Angiopathy / Q000209:etiology*; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology / Q000635:transmission*; D012608:Scrapie / Q000378:metabolism; D012756:Sheep; D013997:Time Factors; D014020:Tissue Extracts / Q000008:administration & dosage / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D014020:Tissue Extracts