{"id":362018,"date":"2026-04-03T14:14:10","date_gmt":"2026-04-03T14:14:10","guid":{"rendered":"https:\/\/www.newsbeep.com\/nz\/362018\/"},"modified":"2026-04-03T14:14:10","modified_gmt":"2026-04-03T14:14:10","slug":"research-shifts-toward-shared-mechanisms-in-neurodegenerative-diseases-newsroom","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/nz\/362018\/","title":{"rendered":"Research Shifts Toward Shared Mechanisms in Neurodegenerative Diseases | Newsroom"},"content":{"rendered":"

Alzheimer\u2019s disease may not be a single illness, but a complex web of overlapping brain disorders that scientists have just started to untangle. Leaders in the field discussed this shift in research at the recent 13th annual Helen and Robert Appel Alzheimer\u2019s Disease Research Institute Symposium held in the Belfer Research Building at Weill Cornell Medicine.<\/p>\n

\u201cThe vision of the Appel Institute is simple. We wanted to tackle some of the most devastating diseases: Alzheimer\u2019s, Parkinson\u2019s, ALS, frontotemporal dementia and some rare neurological disorders,\u201d said Dr. Li Gan<\/a>, director of the Institute at Weill Cornell Medicine, to a crowded room of community members, researchers and clinicians.<\/p>\n

\"Dr.<\/p>\n

Dr. Li Gan<\/p>\n

She emphasized that researchers are now widening their lens\u2014looking for biological connections between neurodegenerative brain diseases to better understand how Alzheimer\u2019s overlaps with conditions like Parkinson\u2019s disease and other forms of dementia.<\/p>\n

That broader perspective is already revealing new clues. Researchers are identifying shared genetic risk factors, uncovering unexpected roles for non-neuronal brain cells and investigating causes upstream of the protein aggregates characteristic of many neurodegenerative diseases.<\/p>\n

\u201cAs we watched the damage from Alzheimer\u2019s affect friends and family, we wanted to find a path to cope with this terrible disease,\u201d said Helen Appel, who helped establish the Institute with her husband in 2006. Their vision has materialized, as researchers and scientists continue to ask hard questions and then follow groundbreaking directions as new data emerges.<\/p>\n

Shared Mechanisms of Neurodegenerative Diseases<\/p>\n

One promising research area focuses on mutations in a gene called GBA, which have been linked to several neurological conditions, including Gaucher\u2019s disease, Parkinson\u2019s disease and dementia with Lewy bodies. Dr. Sreeganga Chandra<\/a>, professor of neurology and neuroscience at Yale University, is uncovering how GBA mutations in concert with other genes affect the brain.<\/p>\n

\"Dr.<\/p>\n

Dr. Sreeganga Chandra<\/p>\n

Patients with a GBA-positive form of Parkinson\u2019s can exhibit faster rates of cognitive decline, even when characteristic protein clumps of \u03b1-synuclein are missing in the brain. While \u03b1-synuclein is critical for normal brain function, these proteins can misfold and aggregate into Lewy bodies, considered a hallmark of not only Parkinson\u2019s disease, but also Lewy body dementia.<\/p>\n

Yet as Dr. Chandra notes, not everyone with GBA mutations, even those who inherit two copies, develops signs of disease. To her, this strongly suggests other genes are protecting or modifying the impact of GBA mutations. Her team is investigating a gene called GANC, which possibly influences \u03b1-synuclein pathology. When GANC activity is artificially increased, \u03b1-synuclein aggregation decreases; and when GANC activity is decreased, aggregation increases.<\/p>\n

\u201cWe are proposing that GANC is an actual modifier of GBA-linked Parkinson\u2019s disease,\u201d she said. \u201cThis is a gene that’s mutated in a large fraction of the Caucasian population, so we think that this may influence the manifestation of the disease.\u201d<\/p>\n

Looking Beyond Neurons<\/p>\n

Neurodegenerative diseases have historically been studied in the context of malfunctioning neurons\u2014specialized, electrically active cells that transmit signals using neurotransmitters to communicate. However, other\u00a0non-neuronal cells<\/a>, such as astrocytes, may be involved. \u00a0These cells support neurons, providing nutrients, structural support, immune defenses and insulation (myelin).\u00a0<\/p>\n

\"\"<\/p>\n

Dr. Anna Orr<\/p>\n

Dr. Anna Orr<\/a>, associate professor at Weill Cornell, is uncovering new insights about astrocytes, which are critical at the synapses where neurons communicate with one another.<\/p>\n

Astrocytes can be affected by abnormalities in a protein called TDP-43, which normally regulates RNA splicing, transcription and other processes involved in making proteins. Pathologies along this pathway are common in frontotemporal dementia (FTD), Alzheimer\u2019s disease and ALS.<\/p>\n

Dr. Orr and her team found that astrocytes with TDP-43 pathology released molecules called chemokines that drive inflammation, causing normal neurons to misfire or over fire. Removing the chemokine gene improved cognitive performance, indicating that the activity of the affected astrocytes was \u201csufficient to cause progressive cognitive decline,\u201d she said.<\/p>\n

Dr. Orr also discussed new research on astrocytes overproducing free radicals in disease and how this process may promote pathology in frontotemporal dementia and Alzheimer\u2019s. Her team discovered that blocking a specific site where free radicals are largely released within astrocytes can effectively lower inflammation and protect neurons, revealing a novel approach to prevent dementia. The Orr lab is developing compounds as potential therapeutics to stop the harm from these oxidative pathways and possibly reverse the course of disease.<\/p>\n

Rethinking the Root Cause<\/p>\n

As the final speaker, Dr. Edward Lee<\/a>, director of the Center for Neurodegenerative Disease Research at the University of Pennsylvania, showed an image of people saving babies from a river, as a lone person walked upstream to find who was tossing the infants into the water. Dr. Lee used this analogy to illustrate that by historically focusing on a single cause, such as amyloid or TDP-43, researchers may have missed a root cause of neurodegenerative diseases.<\/p>\n

Turning to autopsy data, Dr. Lee noted that dementia is not a monolith caused by a single protein or pathology but is complex with many interacting factors. His lab is searching for a common thread in the molecular pathways that are relevant to these diseases.<\/p>\n

He shared the story of a woman who asked for help after her husband and subsequently her three children passed away from an inherited form of dementia. All were found to have a buildup of tau proteins in the brain, \u201ctauopathy,\u201d without amyloid plaques. The family carried a mutation in the VCP gene, which normally helps degrade proteins tagged for disposal with ubiquitin molecules.<\/p>\n

Mutations in VCP may have a link to abnormal protein clumps, including tau and TDP-43, Dr. Lee said. VCP pathologies may not be clearing tau aggregates, for example. Another mutation his lab found may prevent VCP from entering a cell\u2019s nucleus to do its job of removing TDP-43, resulting in the protein accumulating.<\/p>\n

\u201cThis finding suggests a need to activate VCP as a therapeutic to target not just one protein, but in theory any ubiquitinated protein aggregate,\u201d he said.<\/p>\n

The symposium also provided the opportunity for the audience to ask the researchers questions. The scientists spoke about next steps, including increased screening for GBA mutations for patients with Parkinson\u2019s and research aimed at preventing pathogens earlier in life that may trigger neurodegeneration.<\/p>\n

Together, the findings presented at the symposium reflect a growing effort to understand neurodegenerative diseases as interconnected processes with shared biological roots, which may be prevented in the future.<\/p>\n

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