Recent work on Alzheimer's disease transgenics

Current Opinion in Biotechnology

Volumn 9, Issue 6, 1998, Pages 561-564

  Duff, Karen ^a  

^a NATHAN S KLINE INSTITUTE FOR PSYCHIATRIC RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN E; PRESENILIN 1; TAU PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

ALZHEIMER DISEASE; ANIMAL MODEL; BEHAVIOR DISORDER; CHOLINERGIC SYSTEM; CROSSING OVER; DNA FLANKING REGION; HUMAN; MOUSE; NERVE DEGENERATION; NONHUMAN; PRIORITY JOURNAL; SHORT SURVEY; TRANSGENIC MOUSE;

ANIMALIA; MUS MUSCULUS;

EID: 0032402902     PISSN: 09581669     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0958-1669(98)80132-8     Document Type: Article

References (27)

1. Hardy J. Recent advances in the genetics of Alzheimer's disease. Ann Med. 28:1996;255-258.
2. Games D, Adams D, Alessandrini R, Barbour R, Barthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F, et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature. 373:1995;523-527.
3. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G. Correlative memory deficits, Aβ elevation and amyloid plaques in transgenic mice. Science. 274:1996;99-102.
4. Duff K, Eckman C, Zehr C, Yu X, Prada CM, Perez-tur J, Hutton M, Buee L, Harigaya Y, Yager D, et al. Increased amyloid-Aβ42(43) in brains of mice expressing mutant presenilin 1. Nature. 383:1996;710-713.
5. Borchelt DR, Ratovitski T, van Lare J, Lee MK, Gonzales V, Jenkins NA, Copeland NG, Price DL, Sisodia SS. Familial Alzheimer's disease-linked presenilin 1 variants elevate aβ1-42/1-40 ratio in vitro and in vivo. Neuron. 17:1996;1005-1013.
6. Citron M, Westaway D, Xia W, Carlson G, Diehl T, Levesque G, Johnson-Wood K, Lee M, Seubert P, Davis A, et al. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice. Nat Med. 3:1997;67-68.
7. Sturchler-Pierrat C, Abramowski D, Duke M, Wiederhold KH, Mistl C, Rothacher S, Ledermann B, Burki K, Frey P, Paganetti PA, et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. of special interest Proc Natl Acad Sci USA. 94:1997;13287-13292 These mice contained the APP751 cDNA with two AD causing mutations under the control of the thy-1 promoter to drive high level expression of APP. Two lines were generated: one (line 22) had intermediate levels of Aβ and formed diffuse deposits; the other (line 23) generated high levels of Aβ and formed compact amyloid deposits at six months. This study includes reports of limited cell loss, tau hyperphosphorylation and dystrophic cholinergic cells.
8. Nalbantoglu J, Tirado-Santiago G, Lahsaini A, Poirier J, Goncalves O, Verge G, Momoli F, Welner SA, Massicotte G, Julien JP, Shapiro ML. Impaired learning and LTP in mice expressing the carboxy terminus of the Alzheimer amyloid precursor protein. of special interest Nature. 387:1997;500-505 The mouse overexpresses the carboxy-terminal fragment, the Aβ region, of APP. This mouse was reported to show Aβ deposits, cell loss and behavioral impairment. This paper would benefit from confirmation of the phenotype in subsequent publications or similar mice.
9. Johnson-Wood K, Lee M, Motter R, Hu K, Gordon G, Barbour R, Khan K, Gordon M, Tan H, Games D, et al. Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease. Proc Natl Acad Sci USA. 94:1997;1550-1555.
10. Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, DeLong MR. Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science. 215:1982;1237-1239.
11. Lorenzo A, Yankner BA. Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. Proc Natl Acad Sci USA. 91:1994;12243-12247.
12. Irizarry MC, McNamara M, Fedorchak K, Hsiao K, Hyman BT. APPSw transgenic mice develop age-related A-beta deposits and neuropil abnormalities, but no neuronal loss in CA1. J Neuropathol Exp Neurol. 9:1997;965-973.
13. Irizarry MC, Soriano F, McNamara M, Page KJ, Schenk D, Games D, Hyman BT. A-beta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J Neurosci. 17:1997;7053-7059.
14. Geula C, Wu C, Saroff D, Lorenzo A, Yuan M, Yankner B. Aging renders the brain vulnerable to amyloid b-protein neurotoxicity. of outstanding interest Nat Med. 4:1998;827-831 This paper describes a primate model for AD that develops tau abnormalities, Aβ aggregates and cell loss. This paper not only shows that in primates these features can all result from increased local concentrations of amyloid, but also that the lack of these features in rodents may explain why transgenic mice models do not show tau pathology and extensive cell loss. In addition, it suggests that aging may be a required factor for cell loss to occur.
15. Borchelt DR, Ratovitski T, van Lare J, Lee MK, Gonzales V, Jenkins NA, Copeland NG, Price DL, Sisodia SS. Accelerated amyloid deposition in the brains of transgenic mice co-expressing mutant presenilin 1 and amyloid precursor proteins. of special interest Neuron. 4:1997;939-945 This paper and the following one [16] show that amyloid deposition and Aβ concentration are directly linked. The PS1 mice show elevated Aβ42 levels and this slight increase in Aβ greatly accelerates the rate at which Aβ levels in the APP mouse reach deposition levels. Here, APP mice that usually deposit at 18 months showed deposits at nine months in the presence of mutant PS1.
16. Holcomb L, Gordon MN, McGowan E, Yu X, Benkovic S, Jantzen P, Wright K, Saad I, Mueller R, Morgan D, et al. Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. of special interest Nat Med. 1:1998;97-100 APP mice that usually deposit at 12 months deposit at 3-4 months when mutant PS1 is also expressed. Subsequent data shows that this age is reduced to 10-12 weeks with a different PS1 line (E McGowan, personal communication). This model uses the Tg2576 mouse and mutant PS1 mice that are both available to academics and (under license) to industry. The doubly transgenic mice have the most robust and predictable amyloid phenotype yet shown in a transgenic mouse model.
17. Wyss-Coray T, Masliah E, Mallory M, McConlogue L, Johnson-Wood K, Lin C, Mucke L. Amyloidogenic role of cytokine TGF-β1 in transgenic mice and in Alzheimer's disease. Nature. 389:1997;603-606.
18. Corder E, Saunders A, Strittmatter W, Schmechel D, Gaskell P, Small G, Roses A, Haines J, Pericak-Vance MA. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 261:1993;921-923.
19. Corder EH, Saunders AM, Risch NJ, Strittmatter WJ, Schmechel De, Gaskell PC Jr, Rimmler JB, Locke PA, Conneally PM, Schmader KE, et al. Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet. 2:1994;180-184.
20. Bales KR, Verina T, Dodel RC, Du Y, Altstiel L, Bender M, Hyslop P, Johnstone EM, Little SP, Cummins DJ, et al. Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition. of outstanding interest Nat Genet. 3:1997;263-264 This important paper demonstrates that ApoE interacts with amyloid in vivo and has opened the field for more in depth studies of the mechanisms by which ApoE influences AD risk. Modulation of the levels of ApoE is a potential target for drug therapy.
21. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, et al. Diffusible, nonfibrillar ligands derived from Abeta 1-42 are potent central nervous system neurotoxins. of special interest Proc Natl Acad Sci USA. 95:1998;6448-6453 Potential pathogenic mechanism that may have important implications in drug design. The paper suggests that inhibiting Aβ fibril formation (and deposition) may generate toxic Aβ oligomers. Drugs designed to inhibit fibrilogenesis may, therefore, be detrimental in the treatment of AD.
22. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. of special interest Nature. 393:1998;702-705 One of several papers that have identified pathogenic sequence variants in the tau gene that are linked with neurodegeneration and dementia.
23. Justice A, Motter R. Behavioral characterisation of PDAPP transgenic Alzheimer mice. Abstract 636.6, Society for Neurosciences. 1997;. New Orleans.
24. Oyama F, Sawamura N, Kobayashi K, Morishima-Kawashima M, Kuramochi T, Ito M, Tomita T, Maruyama K, Saido TC, Iwatsubo T, et al. Mutant presenilin 2 transgenic mouse: effect on an age-dependent increase of amyloid beta-protein 42 in the brain. of special interest J Neurochem. 71:1998;313-322 The first paper to describe the Aβ effect in PS2 transgenics. This shows that the PS2 mutations also lead to the specific elevation of Aβ42 and as PS2 mutations cause AD, it links Aβ elevation and AD more conclusively.
25. Wong PC, Zheng H, Chen H, Becher MW, Sirinathsinghji DJ, Trumbauer ME, Chen HY, Price DL, Van der Ploeg LH, Sisodia SS. Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature. 387:1997;288-292.
26. Conlon RA, Reaume AG, Rossant J. Notch1 is required for the coordinate segmentation of somites. Development. 121:1995;1533-1545.
27. Levitan D, Doyle TG, Brousseau D, Lee MK, Thinakaran G, Slunt HH, Sisodia SS, Greenwald I. Assessment of normal and mutant human presenilin function in Caenorhabditis elegans. Proc Natl Acad Sci USA. 93:1995;14940-14944.