RETIRED FROM MCGILL - AUGUST 31, 2011
Biology and pathogenesis of Alzheimer's-type and reactive amyloidosis
Lyman Duff Medical Building
3775 University St., Room 402
Montreal, QC H3A 2B4
zafer [dot] ali-khan [at] mcgill [dot] ca (Email)
The clinical condition termed amyloidosis often forms a common link between a number of diverse human diseases such as Alzheimer's disease, Down's syndrome, multiple myeloma, rheumatoid arthritis, and a host of chronic bacterial and parasitic diseases. The common denominator among these diseases is the presence of amyloid deposits in various soft organs. Amyloid is a proteinaceous amorphous substance which infiltrates the extracellular matrix, progressively increases in mass, and thus interferes with normal organ activities.
Recent studies suggest that amyloid deposition in selected brain subregions causes severe loss of neurons and thus plays an important role in Alzheimer's disease pathogenesis. The precise etiopathogenesis of this disease or other forms of systemic amyloidosis is still obscure.
An animal model of reactive amyloidosis, developed in this laboratory, has offered us avenues to examine and identify factors that might be involved in the transformation of otherwise "normal" serum or cellular proteins into amyloid. One such factor is amyloid enhancing factor (AEF). Passive transfer of crude AEF induces amyloid deposition in mice within 48 hours. This factor has been recently identified to be ubiquitin. It is one of the heat-shock or stress proteins. Significantly elevated levels of ubiquitin are present both in Alzheimer brain and amyloidotic murine tissue extracts. How ubiquitin might work in amyloidogenesis remains to be elucidated. It is the focus of our present investigations.
Selected Recent Publications
Ali-Khan Z. "Searching for an in vivo site for nascent amyloid fibril formation." J Alzheimers Dis. 2002 Apr;4(2):105-14.
Qahtani F, Deschenes J, Ali-Khan Z, Maclean JD, Codere F, Mansour M, Burnier M Jr. "Intraocular gnathostomiasis: a rare Canadian case." Can J Ophthalmol. 2000 Feb;35(1):35-9.
Dubois J, Ismail AA, Chan SL, Ali-Khan Z. "Fourier transform infrared spectroscopic investigation of temperature- and pressure-induced disaggregation of amyloid A." Scand J Immunol. 1999 Apr;49(4):376-80.
Bell, A.E., Chan, S.L., and Ali-Khan, Z. (1999). "N-terminal sequence analysis of SAA-derivates purified from murine inflammatory macrophages." Amyloid: International Journal of Experimental and Clinical Investigations 6: 31-36.
Master, E., Chan, S.L., and Ali-Khan, Z. (1998). "Ubiquitin (Ub) interacts non-covalently with Alzheimer amyloid precursor protein (ßPP); isolation of Ub-ßPP conjugates from brain extracts." Alzheimer's Research 4: 19-25.
Ali-Khan, Z., Chan, S.L., Jung, S.S., and Chronopoulos, S. (1996). "Ubiquitin and Alzheimer's amyloid ß-precursor protein colocalize to endosomes-lysosomes in cultured human cells." NeuroReport 7: 1-5.
Ali-Khan, Z., Li, W., and Chan, S.L. (1996). "Animal model for the pathogenesis of reactive amyloidosis." Parasitology Today 12: 297-302.
Chronopoulous, S., Chan, S.L., Ratcliffe, M.J.H., and Ali-Khan, Z. (1995). "Colocalization of ubiquitin and serum amyloid A and ubiquitin-bound AA in the endosomes-lysosomes: A double immunogold electron microscopic study." Amyloid: International Journal of Experimental and Clinical Investigations 2: 191-194.
Chronopoulos, S., Lembo, P., Alizadeh-Khiavi, K., and Ali-Khan, Z. (1991). "Ubiquitin: its potential significance in murine AA amyloidogenesis." Journal of Pathology 163: 199-203.