Romanian Journal of Psychopharmacology (2010) 10, 1-8 PATHOPHYSIOLOGY OF ALZHEIMER’S DISEASE Monica Gheorghita 1 , Iosif Gabos-Grecu 1,2 , Gabriela Buicu 1,2 , Marieta Gabos-Grecu 1,2 , Andreea Salcudean 1 , Ana Maria Todoran 2 1 University Clinic of Psychiatry I Tirgu Mures, Romania 2 University of Medicne and Pharmacy Tirgu Mures, Romania Abstract Introduction. Alzheimer’s disease is a progressive dementia with loss of neurons and the presence of two main microscopic neuropathological hallmarks: extracellular amyloid plaques and intracellular neurofibrillary tangles. Propose. The present study proposes to present the major physiopathological mechanisms involved in the pathogenesis of the Alzheimer’s disease. Material and methods. Review of genetic, pathophysiological and neuropsichopharmacological changes, which occur during on evolution of this disease.The only confirmed risk factors for sporadic AD are age and the presence of the E4 allele of APOE (apolipoprotein E). Amyloid plaques comprise mainly of the neurotoxic peptide amyloid (A beta), cleaved sequentially from a larger precursor protein (APP) by two enzymes: Beta- secretase (also called BACE1) and Gama-secretase (comprising four proteins, one of which is presenilin). If APP is first cleaved by the enzyme alfa-secretase rather than beta-secretase then A- beta is not formed. Neurofibrillary tangles comprise mainly of the protein tau which binds microtubules, thereby facilitating the neuronal transport system. Uncoupling of tau from microtubules and aggregation into tangles inhibits transport and results in microtubule disassembly.Phosphorylation of tau may play an important role in this. Conclusion. Selective vulnerability of neuronal systems such as the cholinergic, serotonergic, noradrenergic and glutamatergic systems form the basis of current rational pharmacological treatment. Key words: Alzheimer’s disease, amyloid plaques, neurofibrillary tangles, apolipoprotein E, tau protein phosphorylation. Introduction Alzheimer’s disease is a progressive dementia with loss of neurons and the presence of two main microscopic neuropathological hallmarks: extracellular amyloid plaques and intracellular neurofibrillary tangles. Propose The present study proposes to present the major physiopathological mechanisms involved in the pathogenesis of the Alzheimer’s disease. 1 Correspondence: Monica Gheorghita, University Clinic of Psychiatry I, Gheorghe Marinescu St. 38, Tg. Mures, Romania. Tel +40 720-999764, e-mail: [email protected]1
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Romanian Journal of Psychopharmacology (2010) 10, 1-8
PATHOPHYSIOLOGY OF ALZHEIMER’S DISEASE
Monica Gheorghita1, Iosif
Gabos-Grecu
1,2, Gabriela Buicu
1,2, Marieta
Gabos-Grecu
1,2,
Andreea Salcudean1, Ana Maria Todoran
2
1University Clinic of Psychiatry I Tirgu Mures, Romania
2University of Medicne and Pharmacy Tirgu Mures, Romania
Abstract Introduction. Alzheimer’s disease is a progressive dementia with loss of neurons and the presence of two main microscopic neuropathological hallmarks: extracellular amyloid plaques and intracellular neurofibrillary tangles. Propose. The present study proposes to present the major physiopathological mechanisms involved in the pathogenesis of the Alzheimer’s disease. Material and methods. Review of genetic, pathophysiological and neuropsichopharmacological changes, which occur during on evolution of this disease.The only confirmed risk factors for sporadic AD are age and the presence of the E4 allele of APOE (apolipoprotein E). Amyloid plaques comprise mainly of the neurotoxic peptide amyloid (A beta), cleaved sequentially from a larger precursor protein (APP) by two enzymes: Beta-secretase (also called BACE1) and Gama-secretase (comprising four proteins, one of which is presenilin). If APP is first cleaved by the enzyme alfa-secretase rather than beta-secretase then A- beta is not formed. Neurofibrillary tangles comprise mainly of the protein tau which binds microtubules, thereby facilitating the neuronal transport system. Uncoupling of tau from microtubules and aggregation into tangles inhibits transport and results in microtubule disassembly.Phosphorylation of tau may play an important role in this. Conclusion. Selective vulnerability of neuronal systems such as the cholinergic, serotonergic, noradrenergic and glutamatergic systems form the basis of current rational pharmacological treatment. Key words: Alzheimer’s disease, amyloid plaques, neurofibrillary tangles, apolipoprotein E, tau protein phosphorylation.
Introduction
Alzheimer’s disease is a progressive dementia with loss of neurons and the presence of two
main microscopic neuropathological hallmarks: extracellular amyloid plaques and intracellular
neurofibrillary tangles.
Propose
The present study proposes to present the major physiopathological mechanisms involved in
the pathogenesis of the Alzheimer’s disease.
1 Correspondence: Monica Gheorghita, University Clinic of Psychiatry I, Gheorghe Marinescu St. 38, Tg. Mures,