Neuropathologic changes in Alzheimer's disease.

Alzheimer's disease is characterized by degenerative changes in a variety of neurotransmitter systems. These include alterations in the function of the monoaminergic neural systems that release glutamate, norepinephrine, and serotonin as well as a few neuropeptide-containing systems. Alzheimer's disease is also characterized by degenerative changes in selected brain regions, including the temporal and parietal lobes and restricted regions within the frontal cortex and cingulate gyrus. The degeneration of these systems may underlie specific aspects of the dementia associated with Alzheimer's disease. A major problem in Alzheimer's disease research today is that none of the current hypothesized mechanisms are able to explain the cellular and regional distribution pattern that characterizes the neuropathology of Alzheimer's disease. This article summarizes the nature and extent of the changes associated with neural systems, possible treatment approaches, and a potential mechanism involving chronic neuroinflammation to explain the pattern of neuropathologic changes in Alzheimer's disease.

[1]  B. Varnum,et al.  TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. , 1991, The Journal of biological chemistry.

[2]  O'Banion Mk Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology. , 1999 .

[3]  M. O’Banion,et al.  Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology. , 1999, Critical reviews in neurobiology.

[4]  J. Rogers Inflammation as a pathogenic mechanism in Alzheimer's disease. , 1995, Arzneimittel-Forschung.

[5]  K. Prasad,et al.  Risk Factors for Alzheimer’s Disease: Role of Multiple Antioxidants, Non-Steroidal Anti-inflammatory and Cholinergic Agents Alone or in Combination in Prevention and Treatment , 2002, Journal of the American College of Nutrition.

[6]  H. Herschman,et al.  Structure of the mitogen-inducible TIS10 gene and demonstration that the TIS10-encoded protein is a functional prostaglandin G/H synthase. , 1992, The Journal of biological chemistry.

[7]  D. Selkoe Alzheimer's disease: genes, proteins, and therapy. , 2001, Physiological reviews.

[8]  E. Sigurdsson,et al.  A safer vaccine for Alzheimer’s disease? , 2002, Neurobiology of Aging.

[9]  B Frangione,et al.  Immunization with a nontoxic/nonfibrillar amyloid-beta homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice. , 2001, The American journal of pathology.

[10]  W. Danysz,et al.  No interaction of memantine with acetylcholinesterase inhibitors approved for clinical use. , 2000, Life sciences.

[11]  G. Wenk,et al.  A nitric oxide-donating flurbiprofen derivative reduces neuroinflammation without interacting with galantamine in the rat. , 2002, European journal of pharmacology.

[12]  V. Winn,et al.  cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[13]  K. Ashe,et al.  Ibuprofen Suppresses Plaque Pathology and Inflammation in a Mouse Model for Alzheimer's Disease , 2000, The Journal of Neuroscience.

[14]  B. Hauss-Wegrzyniak,et al.  Chronic Brain Inflammation Results in Cell Loss in the Entorhinal Cortex and Impaired LTP in Perforant Path-Granule Cell Synapses , 2002, Experimental Neurology.

[15]  V. Winn,et al.  A serum- and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. , 1991, The Journal of biological chemistry.

[16]  Roger N Gunn,et al.  In-vivo measurement of activated microglia in dementia , 2001, The Lancet.

[17]  G. Wenk,et al.  Mechanisms to prevent the toxicity of chronic neuroinflammation on forebrain cholinergic neurons. , 2000, European journal of pharmacology.

[18]  Rong Wang,et al.  A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity , 2001, Nature.

[19]  G. Wenk,et al.  Pathological and biochemical consequences of acute and chronic neuroinflammation within the basal forebrain cholinergic system of rats , 1999, Neuroscience.

[20]  G. Wenk,et al.  The effects of a novel NSAID on chronic neuroinflammation are age dependent☆ , 1999, Neurobiology of Aging.

[21]  P. Kelly,et al.  Cholinergic Changes in the APP23 Transgenic Mouse Model of Cerebral Amyloidosis , 2002, The Journal of Neuroscience.

[22]  C. Lemere,et al.  Inflammatory responses to amyloidosis in a transgenic mouse model of Alzheimer's disease. , 2001, The American journal of pathology.

[23]  P. Aisen Anti-inflammatory agents in Alzheimer’s disease , 2002, Current neurology and neuroscience reports.

[24]  C. Plata-salamán,et al.  Inflammation and Alzheimer’s disease , 2000, Neurobiology of Aging.

[25]  P. Zandi,et al.  Do NSAIDs prevent Alzheimer’s disease? And, if so, why? The epidemiological evidence , 2001, Neurobiology of Aging.

[26]  D. Selkoe,et al.  Deciphering the genetic basis of Alzheimer's disease. , 2002, Annual review of genomics and human genetics.

[27]  L. Rowland,et al.  Merritt's textbook of neurology , 1995 .