Alzheimer Disease: Bari F

Kálmán J, Palotás A, Kis G, Boda K, Túri P, Bari F, Domoki F, Dóda I, Argyelán M, Vincze G, Séra T, Csernay L, Janka Z, Pávics L. · Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, H-6721 Szeged, Semmelweis u. 6, Hungary. · Eur J Neurosci. · Pubmed #15845094 No free full text.

Abstract: Bilateral temporoparietal hypoperfusion is a characteristic single photon emission computed tomography (SPECT) finding in Alzheimer's disease (AD). Lactate is a metabolic vasodilator and is known to provoke increased cerebral blood flow (CBF) in healthy adults. This work investigated whether lactate, which is present in high concentrations in AD cerebrospinal fluid, affects AD-specific perfusion abnormalities. Twenty mild-to-moderately demented AD probands participated in the self-controlled study. The regional CBF was examined utilizing (99m)Tc-HMPAO SPECT after sodium lactate infusion (0.5 M, 5 mL/kg body weight) and 0.9% NaCl infusion, one on each of two separate days. Despite the vasodilatator effects of sodium lactate, AD rCBF patterns did not show increase in temporo-parietal regions after its infusion. AD-specific bi-temporo-parietal reduction in CBF was accompanied by further hypoperfusion in the parieto-occipital areas after the sodium lactate infusion in seven patients, while no CBF changes were observed in the case of the remaining 13 probands. The pattern of the CBF abnormalities was not correlated with the apolipoprotein E genotype. The decreased vascular responsiveness to sodium lactate reflects disturbed vasoregulatory processes in AD and it is unlikely that lactate would have any relevance in the treatment of AD-related cerebral hypoperfusion, but could be used to improve the value of perfusion SPECT in the diagnosis of AD.

Bari F, Tóth-Szuki V, Domoki F, Kálmán J. · Department of Physiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10, Hungary. · Microvasc Res. · Pubmed #16229865 No free full text.

Abstract: Oscillations in laser Doppler signals derived from the forehead and forearm skin were analyzed in 77 healthy probands from 4 various age groups (ranging between 15 and 77 years) and 22 late-onset sporadic Alzheimer's disease (AD) patients. A characteristic pattern of oscillations in the microcirculatory blood flux ( approximately 8 cycles/min, 0.13 Hz) was observed in the forehead skin, the occurrence of which correlated inversely with age (r = 0.80). The occurrence of forehead vasomotion pattern was 100% in the teenagers, whereas it was significantly less in the elderly control subjects (32%) and in the AD patients (18%). Forearm reactive hyperemia was provoked by 1-min occlusion of the brachial artery, and the vascular reactivity was calculated. This phenomenon also proved to be age-dependent, but the process was not related to AD. Our results indicate that the lack of forehead vasomotion reflects aging better than does the forearm vasomotion. Both of these functions are preserved in AD.

Farkas E, Donka G, de Vos RA, Mihály A, Bari F, Luiten PG. · Department of Molecular Neurobiology, University of Groningen, The Netherlands. · Acta Neuropathol. · Pubmed #15138777 No free full text.

Abstract: Though cerebral white matter injury is a frequently described phenomenon in aging and dementia, the cause of white matter lesions has not been conclusively determined. Since the lesions are often associated with cerebrovascular risk factors, ischemia emerges as a potential condition for the development of white matter injury. In the present study, we induced experimental cerebral hypoperfusion by permanent, bilateral occlusion of the common carotid arteries of rats (n=6). A sham-operated group served as control (n=6). Thirteen weeks after the onset of occlusion, markers for astrocytes, microglia, and myelin were found to be labeled by means of immunocytochemistry in the corpus callosum, the internal capsule, and the optic tract. The ultrastructural integrity and oligodendrocyte density in the optic tract were investigated by electron microscopy. Quantitative analysis revealed that chronic cerebral hypoperfusion caused mild astrogliosis in the corpus callosum and the internal capsule, while astrocytic disintegration in the optic tract increased by 50%. Further, a ten-fold increase in microglial activation and a nearly doubled oligodendrocyte density were measured in the optic tract of the hypoperfused rats as compared with the controls. Finally, vacuolization and irregular myelin sheaths were observed at the ultrastructural level in the optic tract. In summary, the rat optic tract appears to be particularly vulnerable to ischemia, probably because of the rat brain's angioarchitecture. Since the detected glial changes correspond with those reported in vascular and Alzheimer dementia, this model of cerebral hypoperfusion may serve to characterize the causal relationship between ischemia and white matter damage.