Certain new aspects of etiology and pathogenesis of Alzheimer’s disease

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DOI: 10.4236/aad.2012.13009    3,313 Downloads   6,964 Views   Citations


The research focuses on the possibility of early detection of AD-specific vascular and atrophic brain changes in families which have a tendency to inherit the disease. The research includedthree families with AD inheritance. All patientsunderwent: cognitive function assessment(MMSE),determination of dementia severity(CDR) and AD stages (TDR), computed tomography (CT), magnetic resonance imaging (MRI), scintigraphy of the brain (SG), rheoencephalography (REG), and cerebral multigated angiography (MUGA). All patients with different AD stages, as well as their descendants, have specific atrophic changes in the temporal lobes of the brain. The degree of these changes increases as AD becomes more severe and ranges from 4% - 8% (TDR-0) to 33% - 62% (TDR-3) of the total mass of a healthy person’s temporal lobes. Simultaneously, thepatients examined have changes of microcirculation manifested by reduction of the capillarybed in the temporal and frontalparietal regions,the development of multiple arteriovenousshunts in the same areas, early venous dumping, anomalous expansion of venoustrunks that receive blood from the arterialvenous shunts, venous stasis on the frontoparietal boundary. Similar changes are found among AD patients’ descendants aged 8 - 11, the only difference being in the degree of temporal lobes atrophy which is 4.7%. This proves that microcirculatory disorders are primary and atrophic changes of the temporal lobes are secondary in AD development. The data obtained indicate that the examination of AD patients’ relatives should begin well before the possible manifestations of the disease, even in childhood. It will allow to reveal the possibility of inheritance and the signs of the disease at the earliest possible stage and to begin its treatment in time.

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Maksimovich, I. (2012) Certain new aspects of etiology and pathogenesis of Alzheimer’s disease. Advances in Alzheimer's Disease, 1, 68-76. doi: 10.4236/aad.2012.13009.


[1] 2011 Alzheimer’s Disease Facts and Figures. http://www.alz.org/downloads/Facts_Figures_2011.pdf
[2] Alzheimer’s Association, Generation Alzheimer’s: The Defining Disease of the Baby Boomers. http://act.alz.org/site/DocServer/ALZ_BoomersReport.pdf?docID=521
[3] Fagan, A., Xiong, C. and Bateman, R., et al. (2011) Plasma and cerebrospinal fluid markers in the DIAN study of autosomal-dominant Alzheimer’s disease. Journal of Alz heimer’s & Dementia, 7, S287. http://www.alzheimersanddementia.com/article/S1552-5260(11)00972-1/fulltext
[4] Perrin, R.J., Craig-Schapiro, R. and Morris, J.C., et al. (2011) Identification and validation of novelcerebrospinal fluid biomarkers for staging early Alzheimer’s disease. PLoS One, 12, e16032. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020224/?tool=pmcentrez
[5] Torack, R.M. (1979) Adult dementia: History, biopsy, pathology. Neurosurgery, 4, 434-442. doi:10.1227/00006123-197905000-00011
[6] Blacker, D., Albert, M.S., Bassett, S.S., Go, R.C., Harrell, L.E. and Folstein, M.F. (1994) Reliability and validity of NINCDS-ADRDA criteria for Alzheimer’s disease. The National Institute of Mental Health Genetics Initiative. Archives of Neurology, 51, 1198-2204. http://www.ncbi.nlm.nih.gov/pubmed/7986174?dopt=Abstract
[7] Corey-Bloom, J., Thal, L. and Galasko, D., et al. (1995) Diagnosis and evaluation of dementia. Neurology, 45, 211-218. http://www.ncbi.nlm.nih.gov/pubmed/7854514
[8] Tiraboschi, P., Hansen, L.A., Thal, L.J. and Corey-Bloom, J. (2004) The importance of neuritic plaques and tangles to the development and evolution of AD. Neurology, 8, 1984-1989. http://www.ncbi.nlm.nih.gov/pubmed/15184601?dopt=Abstract
[9] Morris, J.C. (1993) The clinical dementia rating (CDR): Current version and scoring rules. Neurology, 11, 2412- 2414. http://www.ncbi.nlm.nih.gov/pubmed/8232972
[10] Folstein, M.F., Folstein, S.E. and McHugh, P.R. (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189-198. http://www.ncbi.nlm.nih.gov/pubmed/1202204
[11] Jack, C.R., Bentley, M.D., Twomey, C.K. and Zinsmeister, A.R. (1990) MR Imaging-based volume measurements of the hippocampal formation and anterior temporal lobe: Validation studies. Radiology, 176, 205-209. http://www.ncbi.nlm.nih.gov/pubmed/2353093
[12] Jack, C.R., Petersen, R.C. and Xu, Y.C., et al. (1997) Medial temporal atrophy on MRI in normal aging and very mild Alzheimer’s disease. Neurology, 49, 786-794. http://www.ncbi.nlm.nih.gov/pubmed/9305341
[13] Saykin, A.J., Wishart, H.A. and Rabin, L.A., et al. (2006) Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI. Neurology, 12, 834-842. http://www.ncbi.nlm.nih.gov/pubmed/16966547
[14] Small, B.J., Gagnon, E. and Robinson, B. (2007) Early identification of cognitive deficits: Preclinical Alzheimer’s disease and mild cognitive impairment. Geriatrics, 62, 19-23. http://www.ncbi.nlm.nih.gov/pubmed/17408315
[15] Waldemar, G., Dubois, B. and Emre, M., et al. (2007) Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline. European Journal of Neurology, 14, e1-e26. http://www.ncbi.nlm.nih.gov/pubmed/17222085
[16] Maksimovich, I.V. and Gotman, L.N. (2006) Method of complex radiation diagnostics at preclinical and clinical stages of Alzheimer’s disease. Russian Patent No. 2315559. http://bankpatentov.ru/node/28577
[17] Maksimovich, I.V., Gotman, L.N. and Masyuk, S.M. (2006) Method of determining dimensions of temporal brain lobes in patients suffering from Alzheimer’s disease. Russian Patent No. 2306102. http://worldwide.espacenet.com/publicationDetails/biblio?DB=EPODOC&adjacent=true&locale=en_EP&FT=D&date=20070920&CC=RU&NR=2306102C1&KC=C1
[18] Maksimovich, I.V. (2008) Radiodiagnostics of Alzheimer’s disease. Diagnostics and Intervention Radiology, 2, 27-38. http://www.radiology-di.ru/tom-2-N4-2008.html
[19] Maksimovich, I.V. (2009) Possibilities of modern computed tomography of brain in Alzheimer’s disease diagnosis. The Neurologic Bulletin, 1, 5-10. http://www.infamed.com/nb/1_2009_5-10.pdf
[20] Chiang, G.C. Insel, Ph.S., Tosun, D., Schuff, N., Truran- Sacrey, D., Raptentsetsang, S., Jack, C.R. and Weiner, M.W. (2011) Identifying cognitively healthy elderly individuals with subsequent memory decline by using automated MR temporoparietal volumes. Radiology, 259, 844-851. http://radiology.rsna.org/content/259/3/844
[21] Trojanowski, J.Q., Vandeerstichele, H. and Korecka, M., et al. (2010) Update on the biomarker core of the Alzheimer’s disease neuroimaging initiative subjects. Journal of Alzheimer’s & Dementia, 6, 230-238. http://www.ncbi.nlm.nih.gov/pubmed/20451871
[22] Jack, C., Vemuri, P.H. and Viste, H., et al. (2011) Ordering of Alzheimer’s disease biomarkers. Alzheimer’s & Dementia, 7, S4-S5. doi:10.1016/j.jalz.2011.05.011
[23] Meyer, P.T., Hellwig, S. and Amtage, F., et al. (2011) Dual-biomarker imaging of regional cerebral amyloid load and neuronal activity in dementia with PET and 11C-labeled Pittsburgh compound B. Journal of Nuclear Medicine, 52, 393-400. http://www.ncbi.nlm.nih.gov/pubmed/21321269
[24] Adriaase, A., Sanz-Arigita, E. and Binnewijzend, M., et al. (2011) Molecular markers of Alzheimer’s disease pathology and their relationship with default mode network integrity. Journal of Alzheimer’s & Dementia, 7, S2-S3. http://www.alzheimersanddementia.com/article/S1552-5260(11)00144-0/fulltext
[25] Chételat, G., Villemagne, V.L., Pike, K.E., Ellis, K.A., Ames, D., Masters, C.L. and Rowe, C.C. (2012) Relationship between memory performance and β-amyloid deposition at different stages of Alzheimer’s disease. Neurodegenerative Diseases, 10, 141-144. http://www.ncbi.nlm.nih.gov/pubmed/22301812
[26] Holmes, C., Boche, D. and Wilkinson, D., et al. (2008) Long-term effects of Abeta42 immunisation in Alzheimer’s disease: Follow-up of a randomised, placebocontrolled phase I trial. The Lancet, 372, 216-223. http://www.ncbi.nlm.nih.gov/pubmed/18640458?dopt=Abstract
[27] Morel, F. (1950) An apparently dyshoric and topical angiopathy. Monatsschrift for Psychiatrie Neurologie, 120, 352-357. http://www.ncbi.nlm.nih.gov/pubmed/14806299
[28] Maksimovich, I.V. (2009) Changes in angioarchetectonics of brain at Alzheimer’s disease. The Neurologic Bulletin, 2, 9-14. http://www.infamed.com/nb/2_2009_9-14.pdf
[29] Maksimovich, I.V. (2011) Dyscirculatory angiopathy of Alzheimer’s type. Journal of Behavioral and Brain Science, 1, 57-68. doi:10.4236/jbbs.2011.12008
[30] de la Torre, J.C. (1997) Hemodynamic consequences of deformed microvessels in the brain in Alzheimer’s disease. Annals of New York Acadmy Sciences, 26, 75-91. http://www.ncbi.nlm.nih.gov/pubmed/9329682?dopt=Abstract
[31] Skoog, I., Kalaria, R.N. and Breteler, M.M. (1999) Vascular factors and Alzheimer disease. Alzheimer Disease and Associated Disorders, 13, 106-114. http://www.ncbi.nlm.nih.gov/pubmed?term=Skoog%20I%2C%20Kalaria%20R%20N%2C%20Breteler%20M.M.
[32] Kalaria, R.N. (2000) Vascular factors in Alzheimer’s disease. New York Academy of Sciences, New York. http://books.google.ru/books?id=jHZFAAAAYAAJ&hl=ru&source=gbs_book_similarbooks
[33] Kivipelto, M., Helkala, E.L. and Laakso, M.P., et al. (2001) Midlife vascular risk factors and Alzheimer’s disease in later life: Longitudinal, population based study. British Medical Journal, 322, 1447-1451. http://www.bmj.com/content/322/7300/1447
[34] Kalaria, R.N. (2009) Neurodegenerative disease: Diabetes, microvascular pathology and Alzheimer disease. Nature Reviews. Neurology, 5, 305-306. http://www.ncbi.nlm.nih.gov/pubmed/19498432
[35] Di Iorio, A., Zito, M., Lupinetti, M. and Abate, G. (1999) Are vascular factors involved in Alzheimer’s disease? Facts and theories. Aging, 11, 345-352. http://www.ncbi.nlm.nih.gov/pubmed/10738848
[36] Mielke, M.M., Rosenberg, P.B., Tschanz, J.L. and Cook, L., et al. (2007) Vascular factors predict rate of progresssion in Alzheimer disease. Neurology, 6, 1850-1858. http://www.neurology.org/content/69/19/1850.short
[37] Helzner, E.P., Luchsinger, J.A., Scarmeas, N. and Cosentino, S., et al. (2009) Contribution of vascular risk factors to the progression in Alzheimer disease. Archives of Neurology, 66, 343-348. doi:10.1001/archneur.66.3.343
[38] Weller, R.O., Subash, M., Preston, S.D., Mazanti, I. and Carare, R.O. (2008) Perivascular drainage of amyloidbeta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer’s disease. Brain Pathology, 18, 253-266. http://www.ncbi.nlm.nih.gov/pubmed/18363936
[39] Pezzini, A., Del Zotto, E., Volonghi, I., Giossi, A., Costa, P. and Padovani, A. (2009) Cerebral amyloid angiopathy: A common cause of cerebral hemorrhage. Current Medicinal Chemistry, 16, 2498-2513. doi:10.2174/092986709788682047
[40] de la Torre, J.C. and Stefano, G.B. (2000) Evidence that Alzheimer’s disease is a microvascular disorder: The role of constitutive nitric oxide. Brain Research Reviews, 34, 119-136. doi:10.1016/S0165-0173(00)00043-6
[41] Kalaria, R.N. (2002) Small vessel disease and Alzheimer’s dementia: Pathological considerations. Cerebrovascular Diseases, 13, 48-52. doi:10.1159/000049150
[42] de la Torre, J.C. (2002) Alzheimer disease as a vascular disorder: Nosological evidence. Stroke, 33, 1152-1162. doi:10.1161/01.STR.0000014421.15948.67
[43] Bell, R.D. and Zlokovic, B.V. (2009) Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathologica, 118, 103-113. http://www.ncbi.nlm.nih.gov/pubmed/19319544
[44] Zlokovic, B.V. (2011) Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nature Reviews. Neuroscience, 3, 723-738. http://www.ncbi.nlm.nih.gov/pubmed/22048062
[45] De la Torre, J.C. (2012) A turning point for Alzheimer’s disease? Biofactors, 38, 78-83. doi:10.1002/biof.200
[46] Dhikav, V. and Anand, K.S. (2012) Are vascular factors linked to the development of hippocampal atrophy in Alzheimer’s disease? Journal of Alzheimer’s disease, 32, 711-718. http://www.ncbi.nlm.nih.gov/pubmed/22850312
[47] Baloiannis, S.J. and Baloiannis, I.S. (2012) The vascular factor in Alzheimer’s disease: A study in Golgi technique and electron microscopy. Journal of the Neurological Sciences, 322, 117-121. http://www.jns-journal.com/article/S0022-510X(12)00344-9/abstract
[48] Sagare, A.P., Bell, R.D. and Zlokovic, B.V. (2012) Neurovascular defects and faulty amyloid-β vascular clearance in Alzheimer’s disease. Journal of Alzheimer’s disease, 2, a011452. http://www.ncbi.nlm.nih.gov/pubmed/22751174
[49] Kalaria, R.N., Akinyemi, R. and Ihara, M. (2012) Does vascular pathology contribute to Alzheimer changes? Journal of the Neurological Sciences, 322, 141-147. http://www.ncbi.nlm.nih.gov/pubmed/22884479
[50] Kalaria, R. (2012) The neuropathology of vascular cognitive disorders. Journal of Alzheimer’s & Dementia, 8, P727. doi:10.1016/j.jalz.2012.05.1958
[51] Maksimovich, I.V. and Polyaev, Yu.A. (2010) The importance of early diagnosis of dyscircular angiopathy of Alzheimer’s type in the study of heredity of Alzheimer’s disease. Journal of Alzheimer’s & Dementia, 6, e43. http://www.alzheimersanddementia.com/article/S1552-5260(10)02325-3/fulltext
[52] Maksimovich, I.V. (2012) The tomography dementia rating scale (TDR)—The rating scale of Alzheimer’s disease stages. Health, 4, 712-719. http://www.scirp.org/journal/PaperInformation.aspx?paperID=23257
[53] Maksimovich, I.V. (2012) Vascular factors in Alzheimer’s disease. Health, 4, 735-742. http://www.scirp.org/journal/PaperInformation.aspx?paperID=23274
[54] Maksimovich, I.V. (2012) Endovascular application of low-energy laser in the treatment of dyscirculatory angiopathy of Alzheimer’s type. Journal of Behavioral and Brain Science, 2, 67-81. doi:10.4236/jbbs.2012.21008
[55] Burton, E.J., Barber, R., Mukaetova-Ladinska, E.B., Robson, J., Perry, R.H., Jaros, E., Kalaria, R.N. and O’Brien, T.J. (2009) Medial temporal lobe atrophy on MRI differentiates Alzheimer’s disease from dementia with lewy bodies and vascular cognitive impairment: A prospective study with pathological verification of diagnosis. Brain, 132, 195-203. http://www.ncbi.nlm.nih.gov/pubmed/19022858
[56] World Alzheimer’s Report 2012. http://www.alz.org/documents_custom/world_report_2012_final.pdf

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