Developing Topics

Christopher M. Janney; John G. Westine; Kellyann Niotis; Shannon Helfman; Nicholas Clute-Reinig; Sara Murray; Hollie Hristov; Jannatul Dishary; Danny Angerbauer; Corey Saperia; Alon Seifan; Juan Melendez; Jessica P. Lakis; Licet Valois; Chelsea Brubeck; Skylar Olson; Larissa Silva; Praveen Parthasarathy; Helena Colvee; Philip Sisser; Beth Lewis; Maia Mosse; Diana Saville; Audree Rumberger; Michael McCullough; Richard S. Isaacson

doi:10.1002/alz70861_108643

Developing Topics

Christopher M. Janney
, John G. Westine
, Kellyann Niotis
, Shannon Helfman
, Nicholas Clute-Reinig
, Sara Murray
, Hollie Hristov
, Jannatul Dishary
, Danny Angerbauer
, Corey Saperia
, Alon Seifan
, Juan Melendez
, Jessica P. Lakis
, Licet Valois
, Chelsea Brubeck
, Skylar Olson
, Larissa Silva
, Praveen Parthasarathy
, Helena Colvee
, Philip Sisser

Beth Lewis, Maia Mosse, Diana Saville, Audree Rumberger, Michael McCullough, Richard S. Isaacson

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: This study investigates plasma proteins as potential markers for early detection and intervention of Alzheimer's Disease (AD) and other Neurodegenerative Diseases (NDDs). Participants with a family history of NDDs and minimal neurological symptoms, along with healthy controls, were recruited from five sites in the US and Canada. As of April 23, 2025, 198 participants were recruited, with 81 having longitudinal assessments analyzed. METHOD: Participants receiving preventive neurology or medicine care were divided into two groups: "Intervention 1" for those adhering to over 60% of risk reduction interventions, and "Intervention 2" for those adhering to less than 60%. These were compared to healthy controls and AD controls. NDD risk reduction included lifestyle changes, lipid-lowering agents, GLP1s, HRT, Statins, Zetia, and SSRIs. RESULTS: NULISA testing revealed significant changes in three ratios (Aβ42/40, pTau217/Aβ42, pTau181/Aβ42, Oligo-SNCA/SNCA) for Intervention 1 and two ratios for Intervention 2. Additionally, 34 individual biomarkers changed significantly in Intervention 1 and 26 in Intervention 2. Multi-modal interventions showed the highest number of significant changes. Lumipulse testing showed significant differences in the pTau181/AB42 ratio, Aβ40, Aβ42, pTau181, and pTau217 in Intervention 1, and changes in the pTau181/AB42 ratio, Aβ42, and pTau181 in Intervention 2. Controls showed no significant changes. CONCLUSION: The study concluded that higher compliance to interventions led to more significant changes in protein markers. Multi-modal interventions were most effective. Novel alpha-synuclein markers also changed, potentially aiding in evaluating interventions for Lewy Body Dementia and Parkinson's disease. These markers may serve as future outcome measures for preventive neurology care.

Original language	English
Pages (from-to)	e108643
Journal	Alzheimer's and Dementia
Volume	21
DOIs	https://doi.org/10.1002/alz70861_108643
State	Published - 1 Dec 2025
Externally published	Yes

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10.1002/alz70861_108643

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Janney, C. M., Westine, J. G., Niotis, K., Helfman, S., Clute-Reinig, N., Murray, S., Hristov, H., Dishary, J., Angerbauer, D., Saperia, C., Seifan, A., Melendez, J., Lakis, J. P., Valois, L., Brubeck, C., Olson, S., Silva, L., Parthasarathy, P., Colvee, H., ... Isaacson, R. S. (2025). Developing Topics. Alzheimer's and Dementia, 21, e108643. https://doi.org/10.1002/alz70861_108643

@article{8a65cbaf54f646b8ba7246d0a9b80f6b,

title = "Developing Topics",

abstract = "BACKGROUND: This study investigates plasma proteins as potential markers for early detection and intervention of Alzheimer's Disease (AD) and other Neurodegenerative Diseases (NDDs). Participants with a family history of NDDs and minimal neurological symptoms, along with healthy controls, were recruited from five sites in the US and Canada. As of April 23, 2025, 198 participants were recruited, with 81 having longitudinal assessments analyzed. METHOD: Participants receiving preventive neurology or medicine care were divided into two groups: {"}Intervention 1{"} for those adhering to over 60\% of risk reduction interventions, and {"}Intervention 2{"} for those adhering to less than 60\%. These were compared to healthy controls and AD controls. NDD risk reduction included lifestyle changes, lipid-lowering agents, GLP1s, HRT, Statins, Zetia, and SSRIs. RESULTS: NULISA testing revealed significant changes in three ratios (Aβ42/40, pTau217/Aβ42, pTau181/Aβ42, Oligo-SNCA/SNCA) for Intervention 1 and two ratios for Intervention 2. Additionally, 34 individual biomarkers changed significantly in Intervention 1 and 26 in Intervention 2. Multi-modal interventions showed the highest number of significant changes. Lumipulse testing showed significant differences in the pTau181/AB42 ratio, Aβ40, Aβ42, pTau181, and pTau217 in Intervention 1, and changes in the pTau181/AB42 ratio, Aβ42, and pTau181 in Intervention 2. Controls showed no significant changes. CONCLUSION: The study concluded that higher compliance to interventions led to more significant changes in protein markers. Multi-modal interventions were most effective. Novel alpha-synuclein markers also changed, potentially aiding in evaluating interventions for Lewy Body Dementia and Parkinson's disease. These markers may serve as future outcome measures for preventive neurology care.",

author = "Janney, \{Christopher M.\} and Westine, \{John G.\} and Kellyann Niotis and Shannon Helfman and Nicholas Clute-Reinig and Sara Murray and Hollie Hristov and Jannatul Dishary and Danny Angerbauer and Corey Saperia and Alon Seifan and Juan Melendez and Lakis, \{Jessica P.\} and Licet Valois and Chelsea Brubeck and Skylar Olson and Larissa Silva and Praveen Parthasarathy and Helena Colvee and Philip Sisser and Beth Lewis and Maia Mosse and Diana Saville and Audree Rumberger and Michael McCullough and Isaacson, \{Richard S.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Alzheimer's Association. Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2025",

month = dec,

day = "1",

doi = "10.1002/alz70861\_108643",

language = "English",

volume = "21",

pages = "e108643",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley and Sons Inc.",

}

Janney, CM, Westine, JG, Niotis, K, Helfman, S, Clute-Reinig, N, Murray, S, Hristov, H, Dishary, J, Angerbauer, D, Saperia, C, Seifan, A, Melendez, J, Lakis, JP, Valois, L, Brubeck, C, Olson, S, Silva, L, Parthasarathy, P, Colvee, H, Sisser, P, Lewis, B, Mosse, M, Saville, D, Rumberger, A, McCullough, M & Isaacson, RS 2025, 'Developing Topics', Alzheimer's and Dementia, vol. 21, pp. e108643. https://doi.org/10.1002/alz70861_108643

TY - JOUR

T1 - Developing Topics

AU - Janney, Christopher M.

AU - Westine, John G.

AU - Niotis, Kellyann

AU - Helfman, Shannon

AU - Clute-Reinig, Nicholas

AU - Murray, Sara

AU - Hristov, Hollie

AU - Dishary, Jannatul

AU - Angerbauer, Danny

AU - Saperia, Corey

AU - Seifan, Alon

AU - Melendez, Juan

AU - Lakis, Jessica P.

AU - Valois, Licet

AU - Brubeck, Chelsea

AU - Olson, Skylar

AU - Silva, Larissa

AU - Parthasarathy, Praveen

AU - Colvee, Helena

AU - Sisser, Philip

AU - Lewis, Beth

AU - Mosse, Maia

AU - Saville, Diana

AU - Rumberger, Audree

AU - McCullough, Michael

AU - Isaacson, Richard S.

PY - 2025/12/1

Y1 - 2025/12/1

N2 - BACKGROUND: This study investigates plasma proteins as potential markers for early detection and intervention of Alzheimer's Disease (AD) and other Neurodegenerative Diseases (NDDs). Participants with a family history of NDDs and minimal neurological symptoms, along with healthy controls, were recruited from five sites in the US and Canada. As of April 23, 2025, 198 participants were recruited, with 81 having longitudinal assessments analyzed. METHOD: Participants receiving preventive neurology or medicine care were divided into two groups: "Intervention 1" for those adhering to over 60% of risk reduction interventions, and "Intervention 2" for those adhering to less than 60%. These were compared to healthy controls and AD controls. NDD risk reduction included lifestyle changes, lipid-lowering agents, GLP1s, HRT, Statins, Zetia, and SSRIs. RESULTS: NULISA testing revealed significant changes in three ratios (Aβ42/40, pTau217/Aβ42, pTau181/Aβ42, Oligo-SNCA/SNCA) for Intervention 1 and two ratios for Intervention 2. Additionally, 34 individual biomarkers changed significantly in Intervention 1 and 26 in Intervention 2. Multi-modal interventions showed the highest number of significant changes. Lumipulse testing showed significant differences in the pTau181/AB42 ratio, Aβ40, Aβ42, pTau181, and pTau217 in Intervention 1, and changes in the pTau181/AB42 ratio, Aβ42, and pTau181 in Intervention 2. Controls showed no significant changes. CONCLUSION: The study concluded that higher compliance to interventions led to more significant changes in protein markers. Multi-modal interventions were most effective. Novel alpha-synuclein markers also changed, potentially aiding in evaluating interventions for Lewy Body Dementia and Parkinson's disease. These markers may serve as future outcome measures for preventive neurology care.

AB - BACKGROUND: This study investigates plasma proteins as potential markers for early detection and intervention of Alzheimer's Disease (AD) and other Neurodegenerative Diseases (NDDs). Participants with a family history of NDDs and minimal neurological symptoms, along with healthy controls, were recruited from five sites in the US and Canada. As of April 23, 2025, 198 participants were recruited, with 81 having longitudinal assessments analyzed. METHOD: Participants receiving preventive neurology or medicine care were divided into two groups: "Intervention 1" for those adhering to over 60% of risk reduction interventions, and "Intervention 2" for those adhering to less than 60%. These were compared to healthy controls and AD controls. NDD risk reduction included lifestyle changes, lipid-lowering agents, GLP1s, HRT, Statins, Zetia, and SSRIs. RESULTS: NULISA testing revealed significant changes in three ratios (Aβ42/40, pTau217/Aβ42, pTau181/Aβ42, Oligo-SNCA/SNCA) for Intervention 1 and two ratios for Intervention 2. Additionally, 34 individual biomarkers changed significantly in Intervention 1 and 26 in Intervention 2. Multi-modal interventions showed the highest number of significant changes. Lumipulse testing showed significant differences in the pTau181/AB42 ratio, Aβ40, Aβ42, pTau181, and pTau217 in Intervention 1, and changes in the pTau181/AB42 ratio, Aβ42, and pTau181 in Intervention 2. Controls showed no significant changes. CONCLUSION: The study concluded that higher compliance to interventions led to more significant changes in protein markers. Multi-modal interventions were most effective. Novel alpha-synuclein markers also changed, potentially aiding in evaluating interventions for Lewy Body Dementia and Parkinson's disease. These markers may serve as future outcome measures for preventive neurology care.

UR - https://www.scopus.com/pages/publications/105025738324

U2 - 10.1002/alz70861_108643

DO - 10.1002/alz70861_108643

M3 - Article

C2 - 41434492

AN - SCOPUS:105025738324

SN - 1552-5260

VL - 21

SP - e108643

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

ER -

Developing Topics

Abstract

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