Abstract
The concept of central insulin resistance and dysfunctional insulin signaling in Alzheimer's Disease (AD) has been developed by Siegfried Hoyer in 1985–2000. It is widely recognized that the mechanisms underlying neuronal energy deficiency and in particular to elucidate insulin/insulin receptor cascade deficiencies are some of the most relevant proximate characteristics of sporadic AD. The imbalance between cerebral oxygen utilization and cerebral glucose utilization may cause rise in reactive oxygen species production and this might be causal for synapse degeneration. This concept has been substantiated by work on postmortem Alzheimer brains and has been translated back into the streptozotozin animal model, which has stimulated much further research by other researchers. Finally, the insulin hypothesis of Alzheimer's disease has currently advanced into a potential therapeutic avenue.
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Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A et al (2012) Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol 69(1):29–38
Frölich L, Strauss M, Kornhuber J, Hoyer S, Sorbi S, Riederer P, Amaducci L (1990) Changes in pyruvate dehydrogenase complex (PDHc) activity and [3H]-QNB binding in rat brain subsequent to intracerebroventricular injection of bromopyruvate. J Neural Transm [PD Sect] 2:169–178
Frölich L, Ding A, Hoyer S (1995) Holeboard maze learning deficits in rats and biogenic amines in brain cortex after intracerebroventricular injection of 3-bromopyruvate. Pharmacol Biochem Behavior 51:917–922
Frölich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S, Muschner D, Thalheimer A, Türk A, Hoyer S, Zöchling R, Boissl KW, Jellinger K, Riederer P (1998) Braininsulin and insulin receptors in aging and sporadic Alzheimer’s disease. J Neural Transm 105(4–5):423–438
Frölich L, Blum-Degen D, Riederer P, Hoyer S (1999) A disturbance of the neuronal insulin receptor signal transduction in sporadic Alzheimer’s disease. Ann NY Acad Sci 893:290–294
Gottstein U, Bernsmeier A, Sedlmeyer I (1963) the carbohydrate metabolism of the human brain. I. Studies with substrate-specific enzymatic methods in normal brain circulation. KlinWochenschr 41:943–948
Hoyer S (1986) Senile dementia and Alzheimer’s disease. Brain blood flow and metabolism. Prog Neuropsychopharmacol Biol Psychiatry 10(3–5):447–478
Hoyer S (1991) Abnormalities of glucose metabolism in Alzheimer’s disease. Ann NY Acad Sci 640:53–58
Hoyer S, Becker K (1966) Cerebral blood flow and brain metabolism findings in neuropsychiatric patients. Nervenarzt 37(7):322–324
Hoyer S, Nitsch R (1989) Cerebral excess release of neurotransmitter amino acids subsequent to reduced cerebral glucose metabolism in early-onset dementia of Alzheimer type. J Neural Transm 75(3):227–232
Hoyer S, Oesterreich K, Weinhardt F, Krüger G (1975) Blood flow and oxidative metabolism of the brain in patients with dementia (author’s transl). J Neurol 210(4):227–237
Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Müller-Hill B (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325(6106):733–736
Kety SS, Schmidt CF (1946) Measurement of cerebral blood flow and cerebral oxygen consumption in man. Fed Proc 5:264
Masters CL, Beyreuther K (2006) Alzheimer’s centennial legacy: prospects for rational therapeutic intervention targeting the Abeta amyloid pathway. Brain 129(Pt 11):2823–2839
Nitsch R, Hoyer S (1991) Local action of the diabetogenic drug, streptozotocin, on glucose and energy metabolism in rat brain cortex. Neurosci Lett 128(2):199–202
Plaschke K, Hoyer S (1993) Action of the diabetogenic drug streptozotocin on glycolytic and glycogenolytic metabolism in adult rat brain cortex and hippocampus. Int J Dev Neurosci 11(4):477–483
Reger MA, Craft S (2006) Intranasal insulin administration: a method for dissociating central and peripheral effects of insulin. Drugs Today (Barc) 42(11):729–739
Riederer P (2014) Univ.-Prof. Dr. med. Siegfried Hoyer 1933–2014. J Neural Transm 121(6):565–567
Salkovic-Petrisic M, Knezovic A, Hoyer S, Riederer P (2013) What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease about the therapeutic strategies in Alzheimer’s research. J Neural Transm 120(1):233–252
Wadman M (2012) US Government sets out Alzheimer’s plan. Nature 485(7399):426–427
Wickelgren I (1998) Tracking insulin to the mind. Science 280(5363):517–519
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Frölich, L., Müller, W.E. & Riederer, P. Editorial: Siegfried Hoyer’s concept of Alzheimer pathophysiology. J Neural Transm 122, 495–497 (2015). https://doi.org/10.1007/s00702-015-1371-y
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DOI: https://doi.org/10.1007/s00702-015-1371-y