Microinjection of synthetic amyloid beta-protein in monkey cerebral cortex fails to produce acute neurotoxicity.
The cerebral deposition of amyloid beta protein (A beta P) is an early pathogenetic event in Alzheimer's disease (AD). Recent studies suggest both neurotoxic and neurotrophic effects of A beta P in vitro. Because progressive A beta P deposition and surrounding neuritic dystrophy occur spontaneously in primates, we evaluated the in vivo effects of synthetic A beta P in monkey cortex. Experimental and control (reverse or substituted) peptides were stereotactically injected into multiple neocortical sites of adult rhesus monkeys in a vehicle of either artificial cerebrospinal fluid or acetonitrile. After 2 weeks, all injection sites were identified and characterized. A beta P antibodies specifically detected the injected A beta P1-40 peptide. Serial sections stained with silver and antineurofilament protein demonstrated comparable degrees of degenerating neurons, dystrophic neurites, and axonal spheroids associated with both experimental and control peptide injections. Alz 50 staining was sparse or absent in all sites. Similar results were obtained in an animal killed 3 months after injection. We conclude that specific cellular changes closely resembling the pathology of Alzheimer's disease were not detected in these acute experiments, and that control and experimental A beta P peptides produced indistinguishable effects.
Podlisny
M B
MB
Department of Neurology, Harvard Medical School, Boston, Massachusetts.
Stephenson
D T
DT
Frosch
M P
MP
Tolan
D R
DR
Lieberburg
I
I
Clemens
J A
JA
Selkoe
D J
DJ
D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D008253:Macaca mulatta; D008297:Male; D008845:Microinjections; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000473:pathology*
D016229:Amyloid beta-Peptides