William L. Klein Molecular basis of Alzheimer's disease

Research Interests

Our team’s research concerns Alzheimer’s disease, one of today’s great biomedical problems. Not only of tremendous scientific interest, Alzheimer’s is a disease that affects virtually all families. It is a $200 billion a year epidemic that is predicted to cost $1 trillion a year by 2050. Our projects are positioned to develop new diagnostics and therapeutics that we believe will one day make it possible to effectively treat, and even prevent, Alzheimer’s dementia. 

Our earlier breakthrough discovery of Alzheimer’s neurotoxins, now widely believed to instigate the damage leading to dementia, provides the foundation for a wide range of projects. Our 100+ papers and 34 patents on these toxins, known as amyloid beta oligomers, have been cited over 16,000 times. Current projects encompass a wide, multidisciplinary approach that extends from nanotechnology and protein biochemistry to brain imaging and high throughput drug discovery to studies of neuroinflammation and learning and memory. Our ability to carry out such wide-ranging studies depends on our close collaborations with colleagues at Northwestern and around the world.  Because a rigorous understanding of disease mechanisms is essential for effective therapeutics and diagnostics, we are committed to establishing a comprehensive theory of AD pathogenesis that fully explains the involvement of AβOs in disease onset and progression – from the structure of AβOs, to their etiological origins, to the molecular mechanisms by which they instigate the brain cell damage underlying dementia.

Selected Publications

Neuroprotective astrocyte-derived insulin/insulin-like growth factor 1 stimulates endocytic processing and extracellular release of neuron-bound Aβ oligomers. Pitt J, Wilcox KC, Tortelli V, Pereira Diniz L, Oliveira MS, Dobbins C, Yu X-W, Nandamuri S, Gomes FCA, DiNunno N, Viola KL, De Felice FG, Ferreira ST, and Klein WL. Molecular Biology of the Cell. 2017 October 1;28(20):2623-2636.

Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer’s-Associated Aβ Oligomers. Wilcox KC, Marunde MR, Das A, Velasco PT, Kuhns BD, Marty MT, Jiang H, Luan C-H, Sligar SG, and Klein WL. PLoS ONE. 2015 April 30;10(4):e0125263.

Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis. Viola KL and Klein WL. Acta Neuropathologica. 2015 February;129(2):183-206.

Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease. Viola KL, Sbarboro J, Sureka R, De M, Bicca MA, Wang J, Vasavada S, Satpathy S, Wu S, Joshi H, Velasco PT, MacRenaris K, Waters EA, Lu C, Phan J, Lacor P, Prasad P, Dravid VP, and Klein WL. Nature Nanotechnology. 2015 January;10(1):91-98.

Diffusible, nonfibrillar ligands derived from Aβ1–42 are potent central nervous system neurotoxins. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, and Klein WL. PNAS. 1998 May 26;95(11):6448-6453.

View all publications by William L. Klein listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.