This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wisniewski, T. Articles by Frangione, B. Search for Related Content PubMed PubMed Citation Articles by Wisniewski, T. Articles by Frangione, B.

American Journal of Pathology, Vol 151, 601-610, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

Presenilin-1 is associated with Alzheimer's disease amyloid

T Wisniewski, WK Dowjat, B Permanne, J Palha, A Kumar, G Gallo and B Frangione
Department of Neurology, New York University Medical Center, New York 10016, USA. Thomas.Wisniewski@mcfpo.med.nyu.edu

Mutations in presenilin (PS)-1 and -2, located on chromosome 14 and 1 respectively, are the major association with early-onset familial Alzheimer's disease (FAD). FAD has also been linked to mutations in the amyloid beta precursor protein (beta PP), and the presence of the apolipoprotein E4 allele is a risk factor for late-onset AD. The role of PS in FAD and in sporadic AD is unclear. We previously reported the presence of a PS-1 carboxyl-terminal epitope in neuritic plaques (Wisniewski T, Palha JA, Ghiso J, Frangione B: S182 protein in Alzheimer's disease neuritic plaques. Lancet 1995, 346:1366). In the present study, we examined a number of biochemically different cerebral and systemic amyloidoses, finding the PS-1 carboxy epitope only in association with amyloid beta (A beta) lesions. We confirm the presence of this epitope ultrastructurally in neuritic plaques. In addition, biochemical and amino acid sequence data are presented for an association of the 18-kd carboxy fragment of PS-1 with neuritic plaques with a start at residue 300. Three of the proteins with linkage to AD have now been found as components of neuritic plaques. It remains to be determined whether all of these proteins are involved in the same or different pathological pathway(s) and which of these proteins is the most important for the common, late-onset form of AD.

This article has been cited by other articles:

				J M S PEARCE Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, March 1, 2000; 68(3): 348 - 348. [Full Text] [PDF]

				H. Jacobsen, D. Reinhardt, M. Brockhaus, D. Bur, C. Kocyba, H. Kurt, M. G. Grim, R. Baumeister, and H. Loetscher The Influence of Endoproteolytic Processing of Familial Alzheimer's Disease Presenilin 2 on Abeta 42 Amyloid Peptide Formation J. Biol. Chem., December 3, 1999; 274(49): 35233 - 35239. [Abstract] [Full Text] [PDF]