William L. Klein

About

William L. Klein is a professor in the Interdisciplinary Biological Sciences Graduate Program at Northwestern University. He holds a PhD from the University of California - Los Angeles. His research focuses on the molecular basis of Alzheimer's disease, addressing one of today's significant biomedical challenges. His team investigates the disease's mechanisms, particularly the role of amyloid beta oligomers, which are neurotoxins believed to instigate damage leading to dementia. Klein's work aims to develop new diagnostics and therapeutics to treat and prevent Alzheimer's dementia. Klein's research is multidisciplinary, encompassing nanotechnology, protein biochemistry, brain imaging, high throughput drug discovery, neuroinflammation, and studies of learning and memory. His earlier discovery of Alzheimer's neurotoxins has laid the foundation for extensive research, resulting in over 100 papers and 34 patents, with his work being cited over 16,000 times. His efforts are dedicated to establishing a comprehensive theory of Alzheimer's disease pathogenesis, explaining the involvement of amyloid beta oligomers in disease onset and progression.

Research topics

• Chemistry
• Biology
• Neuroscience
• Cell biology
• Medicine

Selected publications

• Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain

  Proceedings of the National Academy of Sciences · 2020-03-06 · 114 citations

  articleOpen access

  Chronic inflammation during Alzheimer's disease (AD) is most often attributed to sustained microglial activation in response to amyloid-β (Aβ) plaque deposits and cell death. However, cytokine release and microgliosis are consistently observed in AD transgenic animal models devoid of such pathologies, bringing into question the underlying processes that may be at play during the earliest AD-related immune response. We propose that this plaque-independent inflammatory reaction originates from neu…

  PublisherOA PDFDOI

• Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer’s disease

  Nature Communications · 2022-01-10 · 108 citations

  articleOpen access

  Abnormalities in brain glucose metabolism and accumulation of abnormal protein deposits called plaques and tangles are neuropathological hallmarks of Alzheimer's disease (AD), but their relationship to disease pathogenesis and to each other remains unclear. Here we show that succinylation, a metabolism-associated post-translational protein modification (PTM), provides a potential link between abnormal metabolism and AD pathology. We quantified the lysine succinylomes and proteomes from brains of…

  PublisherOA PDFDOI

• Identification of intraneuronal amyloid beta oligomers in locus coeruleus neurons of Alzheimer’s patients and their potential impact on inhibitory neurotransmitter receptors and neuronal excitability

  Neuropathology and Applied Neurobiology · 2020-10-29 · 48 citations

  articleOpen access

  Abstract Aims Amyloid β‐oligomers (AβO) are potent modulators of Alzheimer's pathology, yet their impact on one of the earliest brain regions to exhibit signs of the condition, the locus coeruleus (LC), remains to be determined. Of particular importance is whether AβO impact the spontaneous excitability of LC neurons. This parameter determines brain‐wide noradrenaline (NA) release, and thus NA‐mediated brain functions, including cognition, emotion and immune function, which are all compromised i…

  PublisherOA PDFDOI

• Induction of inverted morphology in brain organoids by vertical-mixing bioreactors

  Communications Biology · 2021-10-22 · 35 citations

  articleOpen access

  Organoid technology provides an opportunity to generate brain-like structures by recapitulating developmental steps in the manner of self-organization. Here we examined the vertical-mixing effect on brain organoid structures using bioreactors and established inverted brain organoids. The organoids generated by vertical mixing showed neurons that migrated from the outer periphery to the inner core of organoids, in contrast to orbital mixing. Computational analysis of flow dynamics clarified that,…

  PublisherOA PDFDOI

• The Therapeutic and Diagnostic Potential of Amyloid β Oligomers Selective Antibodies to Treat Alzheimer’s Disease

  Frontiers in Neuroscience · 2022-01-03 · 29 citations

  articleOpen accessSenior author

  imaging methods that allow for the detection of pathological changes in AD by magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Many of these imaging methods, however, use agents that probe amyloid fibrils and plaques-species that do not correlate well with disease progression and are not present at the earliest stages of the disease. Amyloid β oligomers (AβOs), rather, are now widely accepted as the Aβ species most germane to AD onset and progression. Here we report…

  PublisherDOI

Recent grants

• Sporadic Alzheimer's Disease modeled with diabetes and high cholesterol in rabbit

  NIH · $762k · 2018–2020

• NIH Grant R01NS021234

  NIH · $936k · 1993

• Development of a non-fibrillic amyloid-beta oligomer selective positron emission tomography imaging diagnostic for Alzheimer.

  NIH · $222k · 2016–2018

Frequent coauthors

• Sam Gandy

  Icahn School of Medicine at Mount Sinai

  105 shared

• Charles Glabe

  University of California, Irvine

  105 shared

• Michelle E. Ehrlich

  Icahn School of Medicine at Mount Sinai

  103 shared

• Elysse M. Knight

  University of California, San Diego

  102 shared

• Soong Ho Kim

  Icahn School of Medicine at Mount Sinai

  102 shared

• John Steele

  Baylor College of Medicine

  101 shared

• Jessica Kottwitz

  New York University

  101 shared

• Akinobu Suzuki

  Toho University

  100 shared

Similar researchers at Northwestern University

• Brian M. Hoffmanh-112
• Neil L. Kelleherh-110
• Luís A. Nunes Amaralh-101