NG06840
DNA from Fibroblast
Description:
ALZHEIMER DISEASE, FAMILIAL, TYPE 3
PRESENILIN 1; PSEN1
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Repository
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NIA Aging Cell Culture Repository
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| Subcollection |
Canadian Alzheimer Disease |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Arm
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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DNA from Fibroblast
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Race
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White
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Ethnicity
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CANADIAN
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Family Member
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20
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Relation to Proband
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VII-13
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
4.66 |
| Passage Frozen |
9 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis and by Chromosome Analysis |
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| Gene |
PSEN1 |
| Chromosomal Location |
14q24.3 |
| Allelic Variant 1 |
104311.0003; ALZHEIMER DISEASE, FAMILIAL, TYPE 3 |
| Identified Mutation |
ALA246GLU; In a pedigree with chromosome 14-linked early-onset Alzheimer disease, Sherrington et al. [Nature 375: 754-760 (1995)] identified an ala246-to-glu mutation in the novel gene they isolated from the region of chromosome 14 identified by linkage studies as containing the AD3 gene. |
| Remarks |
The donor at time of biopsy was oriented only to the year, had poor recent memory, was unable to do simple subtraction, and had regressive reflexes. He admitted to 6 months of increasing difficulty with memory, although a previous neuro exam at age 52 revealed problems with recent memory. The skin biopsy was taken ante-mortem from the forearm. Culture was initiated on 05/4/83 using explants of minced skin. The cell morphology is fibroblast-like. The culture is a mosaic with karyotype: 46,XY/46,XY, t(2;14)(2qter>2p11.2::14p11.2>14pter;14qter>14p11.2::2p11.2>2pter); balanced; 90%/10%. Culture was frozen at PDL 11. A lymphoblast culture with a 46,XY karotype from this same donor is AG06841A. Cells carry missense mutation {Ala246Glu (A246E)} in the AD3 [presenilin 1 (PSEN1)] gene. The legacy karyotype description shown in this Remark may not be representative of the current available product. |
| Caldwell AB, Liu Q, Zhang C, Schroth GP, Galasko DR, Rynearson KD, Tanzi RE, Yuan SH, Wagner SL, Subramaniam S, Endotype reversal as a novel strategy for screening drugs targeting familial Alzheimer's disease Alzheimer's & dementia : the journal of the Alzheimer's Association: 2021 |
| PubMed ID: 35084109 |
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| Mollinari C, De Dominicis C, Lupacchini L, Sansone L, Caprini D, Casciola CM, Wang Y, Zhao J, Fini M, Russo M, Garaci E, Merlo D, Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons International journal of molecular sciences23: 2021 |
| PubMed ID: 35216271 |
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| Raska J, Hribkova H, Klimova H, Fedorova V, Barak M, Barta T, Pospisilova V, Vochyanova S, Vanova T, Bohaciakova D, Generation of six human iPSC lines from patients with a familial Alzheimer's disease (n = 3) and sex- and age-matched healthy controls (n = 3) Stem cell research53:102379 2021 |
| PubMed ID: 34088008 |
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| Iannuzzi F, Frisardi V, Annunziato L, Matrone C, Might Fibroblasts from Patients with Alzheimer's Disease Reflect the Brain Pathology? A Focus on the Increased Phosphorylation of Amyloid Precursor Protein Tyr Brain sciences11:102379 2020 |
| PubMed ID: 33466666 |
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| Joshi AU, Van Wassenhove LD, Logas KR, Minhas PS, Andreasson KI, Weinberg KI, Chen CH, Mochly-Rosen D, Aldehyde dehydrogenase 2 activity and aldehydic load contribute to neuroinflammation and Alzheimer's disease related pathology Acta neuropathologica communications7:190 2019 |
| PubMed ID: 31829281 |
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| Greotti E, Capitanio P, Wong A, Pozzan T, Pizzo P, Pendin D, Familial Alzheimer's disease-linked presenilin mutants and intracellular Ca Cell calcium79:44-56 2018 |
| PubMed ID: 30822648 |
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| Gonzalez C, Armijo E, Bravo-Alegria J, Becerra-Calixto A, Mays CE, Soto C, Modeling amyloid beta and tau pathology in human cerebral organoids Molecular psychiatry79:44-56 2017 |
| PubMed ID: 30171212 |
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| Coffey EE, Beckel JM, Laties AM, Mitchell CH, Lysosomal alkalization and dysfunction in human fibroblasts with the Alzheimer's disease-linked presenilin 1 A246E mutation can be reversed with cAMP Neuroscience79:44-56 2014 |
| PubMed ID: 24418614 |
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| Lee JH, Yu WH, Kumar A, Lee S, Mohan PS, Peterhoff CM, Wolfe DM, Martinez-Vicente M, Massey AC, Sovak G, Uchiyama Y, Westaway D, Cuervo AM, Nixon RA, Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations Cell141:1146-58 2008 |
| PubMed ID: 20541250 |
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| Nelson O, Tu H, Lei T, Bentahir M, de Strooper B, Bezprozvanny I, Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1 The Journal of clinical investigation117:1230-9 2006 |
| PubMed ID: 17431506 |
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| Parshad RP, Sanford KK, Price FM, Melnick LK, Nee LE, Schapiro MB, Tarone RE, Robbins JH, Fluorescent light-induced chromatid breaks distinguish Alzheimer disease cells from normal cells in tissue culture. Proc Natl Acad Sci U S A93:5146-50 1996 |
| PubMed ID: 8643543 |
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| Kim CS, Han YF, Etcheberrigaray R, Nelson TJ, Olds JL, Yoshioka T, Alkon DL, Alzheimer and beta-amyloid-treated fibroblasts demonstrate a decrease in a memory-associated GTP-binding protein, Cp20. Proc Natl Acad Sci U S A92:3060-4 1995 |
| PubMed ID: 7708775 |
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| Martins RN, Turner BA, Carroll RT, Sweeney D, Kim KS, Wisniewski HM, Blass JP, Gibson GE, Gandy S, High levels of amyloid-beta protein from S182 (Glu246) familial Alzheimer's cells. Neuroreport7:217-20 1995 |
| PubMed ID: 8742455 |
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| Querfurth HW, Wijsman EM, St George-Hyslop PH, Selkoe DJ, Beta APP mRNA transcription is increased in cultured fibroblasts from the familial Alzheimer's disease-1 family. Brain Res Mol Brain Res28(2):319-37 1995 |
| PubMed ID: 7723630 |
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| Etcheberrigaray E, Gibson GE, Alkon DL, Molecular mechanisms of memory and the pathophysiology of Alzheimer's disease. Ann N Y Acad Sci747:245-55 1994 |
| PubMed ID: 7847674 |
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| Ito E, Oka K, Etcheberrigaray R, Nelson TJ, McPhie DL, Tofel-Grehl B, Gibson GE, Alkon DL, Internal Ca2+ mobilization is altered in fibroblasts from patients with Alzheimer disease. Proc Natl Acad Sci U S A91:534-8 1994 |
| PubMed ID: 8290560 |
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| Etcheberrigaray R, Ito E, Oka K, Tofel-Grehl B, Gibson GE, Alkon DL, Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease. Proc Natl Acad Sci U S A90:8209-13 1993 |
| PubMed ID: 8367484 |
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| St George-Hyslop PH, Tanzi RE, Polinsky RJ, Haines JL, Nee L, Watkins PC, Myers RH, Feldman RG, Pollen D, Drachman D, et al, The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science235:885-90 1987 |
| PubMed ID: 2880399 |
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| Nee LE, Polinsky RJ, Eldridge R, Weingartner H, Smallberg S, Ebert M, A family with histologically confirmed Alzheimer's disease. Arch Neurol40:203-8 1983 |
| PubMed ID: 6600923 |
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