Nerve growth factor affects 11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (case report).
Based on animal research suggesting that nerve growth factor (NGF) can stimulate central cholinergic neurons, the known losses of cholinergic innervation of the cortices in Alzheimer's disease (AD), and our experience of infusing NGF to support adrenal grafts in parkinsonian patients, we have initiated clinical trials of NGF infusions into the brain of patients with AD. Here we report a follow-up of our first case, a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF during three months resulted in a marked transient increase in uptake and binding of 11C-nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects could be ascribed to the NGF infusion. Taken together, the results of this case study indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted.
Olson
L
L
Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden.
Nordberg
A
A
von Holst
H
H
Bäckman
L
L
Ebendal
T
T
Alafuzoff
I
I
Amberla
K
K
Hartvig
P
P
Herlitz
A
A
Lilja
A
A
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology; D000440:Butanols; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D007276:Injections, Intraventricular; D008568:Memory / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D019635:Neurosurgical Procedures; D009538:Nicotine / Q000378:metabolism*; D013702:Temporal Lobe / Q000098:blood supply / Q000378:metabolism; D014055:Tomography, Emission-Computed
D000440:Butanols; D002250:Carbon Radioisotopes; D009414:Nerve Growth Factors; D009538:Nicotine