9. Marco Teórico Conceptual
9.2 Procesos de Enseñanza y Aprendizaje
9.2.1 Rol del maestro en la enseñanza
could be in linkage disequilibrium with theA2M-2or
Val-1000-Ile polymorphism. Further studies are
needed to determine the correlation of intronic dele-
tion or Val-1000-Ile polymorphism in
A2M
with AD
in various ethnic backgrounds. This may clarify the
effect of A2M on the development of AD.
Acknowledgment
The authors thank I. Isahai, M. Takeda, and H. Konuma for their expert technical assistance.
References
1. Roses AD. Apolipoprotein E genotyping in the differential di- agnosis, not prediction, of Alzheimer’s disease. Ann Neurol 1995;38:6 –14.
2. Sodeyama N, Itoh Y, Suematsu N, et al. Presenilin 1 intronic polymorphism is not associated with Alzheimer type neuro- pathological changes or sporadic Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1998;64:548 –551.
3. Sodeyama N, Yamada M, Itoh Y, et al. Lack of genetic associ- ations of alpha-1-antichymotrypsin polymorphism with
Table 2A2Mgenotypes and the densities of senile plaques (SPs), SPs with dystrophic neurites (NPs), and neurofibrillary tangles (NFTs) in the hippocampus and superior temporal gyrus in AD and nondemented patients, and age at onset and duration of illness in AD
A2Mgenotype AD (n562) Nondemented (n590) A2M-1/A2M-1 (n559) A2M-1/A2M-2 (n53) pValue A2M-1/A2M-1 (n582) A2M-1/A2M-2 (n58) pValue Hippocampus SPs 19.6611.1 12.663.6 0.23 2.265.6 1.764.8 0.47 NPs 18.0611.2 12.663.6 0.42 1.664.4 1.764.8 0.52 NFTs 47.5629.1 45.8619.0 0.82 4.068.0 2.063.0 0.38
Superior temporal gyrus
SPs 74.0631.4 76.8656.4 0.77 9.3624.5 2.667.3 0.33
NPs 20.9620.4 12.768.5 0.61 1.863.8 1.062.9 0.26
NFTs 5.868.0 4.265.9 0.69 0.060.1 0.060.0 0.53
Age at onset, y 79.368.1 81.367.8 0.42
Duration of illness, y 6.363.9 7.064.6 0.74
Values are medians6SD. The density represents the average counts in 2.56 mm2for SPs and NPs, and in 0.64 mm2for NFTs. A2M5 a2-macroglobulin gene;A2M-15normal allele;A2M-25deletion mutant allele.
Alzheimer-type neuropathological changes or sporadic Alzhei- mer’s disease. Dement Geriatr Cogn Disord 1999;10:221–225. 4. Wragg M, Hutton M, Talbot C, the Alzheimer’s disease Collab- orative Group. Genetic association between intronic polymor- phism in presenilin-1 gene and late-onset Alzheimer’s disease. Lancet 1996;347:509 –512.
5. Kamboh MI, Sanghera DK, Ferrell RE, DeKosky ST. APOE*4- associated Alzheimer’s disease risk is modified by a1- antichymotrypsin polymorphism. Nat Genet 1995;10:486 – 488.
6. Lehmann DJ, Johnston C, Smith AD. Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer’s disease. Hum Mol Genet 1997;6:1933–1936.
7. Wavrant-DeVrie`ze F, Pe´rez-Tur J, Lambert J-C, et al. Associ- ation between the low density lipoprotein receptor-related pro- tein (LRP) and Alzheimer’s disease. Neurosci Lett 1997;227: 68 –70.
8. Narita M, Holtzman DM, Schwartz AL, Bu G. a2- Macroglobulin complexes with and mediates the endocytosis ofb-amyloid peptides via cell surface low-density lipoprotein receptor-related protein. J Neurochem 1997;69:1904 –1911. 9. Ganter U, Strauss S, Jonas U, et al. Alpha 2-macroglobulin
synthesis in interleukin-6-stimulated human neuronal (SH- SY5Y neuroblastoma) cells: potential significance for the pro- cessing of Alzheimerb-amyloid precursor protein. FEBS Lett 1991;282:127–131.
10. Rebeck GW, Harr SD, Strickland DK, Hyman BT. Multiple, diverse senile plaque-associated proteins are ligands of an apolipoprotein E receptor, thea2-macroglobulin receptor/low- density-lipoprotein receptor-related protein. Ann Neurol 1995; 37:211–217.
11. Hughes SR, Khorkova O, Goyal S, et al. a2-Macroglobulin associates withb-amyloid peptide and prevents fibril forma- tion. Proc Natl Acad Sci USA 1998;95:3275–3280.
12. Du Y, Bales KR, Dodel RC, et al.a2-Macroglobulin attenuates b-amyloid peptide 1-40 fibril formation and associated neuro- toxicity of cultured fetal rat cortical neurons. J Neurochem 1998;70:1182–1188.
13. Wood JA, Wood PL, Ryan R, et al. Cytokine indices in Alzhei- mer’s temporal cortex: no changes in mature IL-1bor IL-1RA but increases in the associated acute phase proteins IL-6, a2-macroglobulin and C-reactive protein. Brain Res 1993;629: 245–252.
14. Strauss S, Bauer J, Ganter U, Jonas U, Berger M, Volk B. Detection of interleukin-6 anda2-macroglobulin immunoreac- tivity in cortex and hippocampus of Alzheimer’s disease pa- tients. Lab Invest 1992;66:223–230.
15. Blacker D, Wilcox MA, Laird NM, et al. Alpha-2 macroglobu-
lin is genetically associated with Alzheimer’s disease. Nat Genet 1998;19:357–360.
16. Liao A, Nitsch RM, Greenberg SM, et al. Genetic association of an a2-macroglobulin (Val1000Ile) polymorphism and Alz- heimer’s disease. Hum Mol Genet 1998;7:1953–1956. 17. Kan C-C, Solomon E, Belt KT, Chain AC, Hiorns LR, Fey G.
Nucleotide sequence of cDNA encoding human a2- macroglobulin and assignment of the chromosomal locus. Proc Natl Acad Sci USA 1985;82:2282–2286.
18. Pericak-Vance MA, Bass MP, Yamaoka LH, et al. Complete genomic screen in late-onset familial Alzheimer disease: evi- dence for a new locus on chromosome 12. JAMA 1997;278: 1237–1241.
19. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. Washington DC: Ameri- can Psychiatric Association, 1987.
20. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939 –944.
21. Mirra SS, Heyman A, McKeel D, et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alz- heimer’s disease. Neurology 1991;41:479 – 486.
22. Yamada M, Itoh Y, Otomo E, Suematsu N, Matsushita M. Dementia of the Alzheimer type and related dementias in the aged: DAT subgroups and senile dementia of the neurofibril- lary tangle type. Neuropathology 1996;16:89 –98.
23. Matthijs G, Marynen P. A deletion polymorphism in the hu- man alpha-2-macroglobulin (A2M) gene. Nucleic Acids Res 1991;19:5102.
24. Hixson JE, Vernier DT. Restriction isotyping of human apoli- poprotein E by gene amplification and cleavage withHhaI. J Lipid Res 1990;31:545–548.
25. Dow DJ, Lindsey N, Cairns NJ, et al.a-2 Macroglobulin poly- morphism and Alzheimer disease risk in the UK. Nat Genet 1999;22:16 –17.
26. Rudrasingham V, Wavrant-De Vrie`ze F, Lambert J-C, et al. a-2 Macroglobulin gene and Alzheimer disease. Nat Genet 1999;22:17–19.
27. Rogaeva EA, Premkumar S, Grubber J, et al. An a-2- macroglobulin insertion– deletion polymorphism in Alzheimer disease. Nat Genet 1999;22:19 –21.
28. Wavrant-DeVrie`ze F, Rudrasingham V, Lambert J-C, et al. No association between the alpha-2 macroglobulin I1000V polymorphism and Alzheimer’s disease. Neurosci Lett 1999; 262:137–139.