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Article ; Online: Preclinical Alzheimer's disease: how to predict who will decline next year?

Hanseeuw, Bernard J / Johnson, Keith A

Brain communications

2023 Volume 5, Issue 2, Page(s) fcad079

Abstract: This scientific commentary refers to 'Medial temporal tau predicts memory decline in cognitively unimpaired elderly', by ... ...

Abstract	This scientific commentary refers to 'Medial temporal tau predicts memory decline in cognitively unimpaired elderly', by Kwan
Language	English
Publishing date	2023-03-21
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcad079
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Article ; Online: Impairments of saccadic and reaching adaptation in essential tremor are linked to movement execution.

Blondiaux, Florence / Lebrun, Louisien / Hanseeuw, Bernard J / Crevecoeur, Frédéric

Journal of neurophysiology

2023 Volume 130, Issue 5, Page(s) 1092–1102

Abstract: Essential tremor (ET) is a neurological disorder characterized by involuntary oscillations of the limbs. Previous studies have hypothesized that ET is a cerebellar disorder and reported impairments in motor adaptation. However, recent advances have ... ...

Abstract	Essential tremor (ET) is a neurological disorder characterized by involuntary oscillations of the limbs. Previous studies have hypothesized that ET is a cerebellar disorder and reported impairments in motor adaptation. However, recent advances have highlighted that motor adaptation involves several components linked to anticipation and control, all dependent on cerebellum. We studied the contribution of both components in adaptation to better understand the adaptation impairments observed in ET from a behavioral perspective. To address this question, we investigated behavioral markers of adaptation in ET patients (
MeSH term(s)	Humans ; Essential Tremor ; Movement ; Upper Extremity ; Cerebellum
Language	English
Publishing date	2023-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00165.2023
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Article ; Online: Study Partner Report of Apathy in Older Adults is Associated with AD Biomarkers: Findings from the Harvard Aging Brain Study.

Burling, Jessa E / Katz, Zoe / Yuan, Ziwen / Munro, Catherine / Mimmack, Kayden / Ma, Grace / Hanseeuw, Bernard J / Papp, Kathryn V / Amariglio, Rebecca E / Vannini, Patrizia / Rentz, Dorene M / Quiroz, Yakeel T / Johnson, Keith A / Sperling, Reisa A / Blacker, Deborah / Marshall, Gad A / Yang, Hyun-Sik / Gatchel, Jennifer R

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry

2024

Abstract: Objectives: We examined relationships between apathy (self and study-partner-reported) and markers of Alzheimer's disease (AD) in older adults.: Design: The study utilized a well-characterized sample of participants from the Harvard Aging Brain Study ...

Abstract	Objectives: We examined relationships between apathy (self and study-partner-reported) and markers of Alzheimer's disease (AD) in older adults. Design: The study utilized a well-characterized sample of participants from the Harvard Aging Brain Study (HABS), a longitudinal cohort study. Participants were cognitively unimpaired without clinically significant neuropsychiatric symptoms at HABS baseline. The dependent variables, apathy evaluation scale-self (AES-S) and informant (AES-I), were administered cross-sectionally between years 6-9 and compared to the independent variables, amyloid and tau PET neuroimaging, from the same year. Setting: Community-dwelling participants assessed at research visits in an academic medical center. Participants: Participants (n = 170) completed assessments within 1.5 years of their neuroimaging visit. At the time of apathy assessment, N = 156 were cognitively unimpaired and 14 had progressed to mild cognitive impairment (n = 8) or dementia (n = 6). Measurements: We utilized linear regression models to assess cross-sectional associations of AES-S and AES-I with AD PET imaging measures (beta-amyloid (Pittsburgh Compound B) and tau (Flortaucipir)), covarying for age, sex, education, and the time between PET scan-apathy assessment. Results: AES-I was significantly associated with beta-amyloid and temporal lobe tau, and the associations were retained after further adjusting for depressive symptoms. The associations between AES-S and AD biomarkers were not significant. In an exploratory subgroup analysis of cognitively unimpaired individuals with elevated Aβ, we observed an association between AES-I and inferior temporal tau. Conclusions: Study-partner-reported, but not self-reported, apathy in older adults is associated with AD pathology, and we observed this relationship starting from the preclinical stage. Our findings highlight the importance of collateral information in capturing AD-related apathy.
Language	English
Publishing date	2024-01-28
Publishing country	England
Document type	Journal Article
ZDB-ID	1278145-9
ISSN	1545-7214 ; 1064-7481
ISSN (online)	1545-7214
ISSN	1064-7481
DOI	10.1016/j.jagp.2024.01.020
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Article ; Online: Specific post-translational modifications of soluble tau protein distinguishes Alzheimer's disease and primary tauopathies.

Kyalu Ngoie Zola, Nathalie / Balty, Clémence / Pyr Dit Ruys, Sébastien / Vanparys, Axelle A T / Huyghe, Nicolas D G / Herinckx, Gaëtan / Johanns, Manuel / Boyer, Emilien / Kienlen-Campard, Pascal / Rider, Mark H / Vertommen, Didier / Hanseeuw, Bernard J

Nature communications

2023 Volume 14, Issue 1, Page(s) 3706

Abstract: Tau protein aggregates in several neurodegenerative disorders, referred to as tauopathies. The tau isoforms observed in post mortem human brain aggregates is used to classify tauopathies. However, distinguishing tauopathies ante mortem remains ... ...

Abstract	Tau protein aggregates in several neurodegenerative disorders, referred to as tauopathies. The tau isoforms observed in post mortem human brain aggregates is used to classify tauopathies. However, distinguishing tauopathies ante mortem remains challenging, potentially due to differences between insoluble tau in aggregates and soluble tau in body fluids. Here, we demonstrated that tau isoforms differ between tauopathies in insoluble aggregates, but not in soluble brain extracts. We therefore characterized post-translational modifications of both the aggregated and the soluble tau protein obtained from post mortem human brain tissue of patients with Alzheimer's disease, cortico-basal degeneration, Pick's disease, and frontotemporal lobe degeneration. We found specific soluble signatures for each tauopathy and its specific aggregated tau isoforms: including ubiquitination on Lysine 369 for cortico-basal degeneration and acetylation on Lysine 311 for Pick's disease. These findings provide potential targets for future development of fluid-based biomarker assays able to distinguish tauopathies in vivo.
MeSH term(s)	Humans ; tau Proteins/metabolism ; Alzheimer Disease/diagnosis ; Alzheimer Disease/metabolism ; Pick Disease of the Brain/metabolism ; Corticobasal Degeneration ; Lysine/metabolism ; Tauopathies/diagnosis ; Tauopathies/metabolism ; Protein Isoforms/metabolism ; Brain/metabolism ; Protein Processing, Post-Translational
Chemical Substances	tau Proteins ; Lysine (K3Z4F929H6) ; Protein Isoforms
Language	English
Publishing date	2023-06-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-39328-1
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Article ; Online: Depressive symptoms and hippocampal volume in autosomal dominant Alzheimer's disease.

Langella, Stephanie / Lopera, Francisco / Baena, Ana / Fox-Fuller, Joshua T / Munera, Diana / Martinez, Jairo E / Giudicessi, Averi / Vannini, Patrizia / Hanseeuw, Bernard J / Marshall, Gad A / Quiroz, Yakeel T / Gatchel, Jennifer R

Alzheimer's & dementia : the journal of the Alzheimer's Association

2023 Volume 20, Issue 2, Page(s) 986–994

Abstract: Introduction: Depressive symptoms are among early behavioral changes in Alzheimer's disease (AD); however, the relationship between neurodegeneration and depressive symptoms remains inconclusive. To better understand this relationship in preclinical AD, ...

Abstract	Introduction: Depressive symptoms are among early behavioral changes in Alzheimer's disease (AD); however, the relationship between neurodegeneration and depressive symptoms remains inconclusive. To better understand this relationship in preclinical AD, we examined hippocampal volume and depressive symptoms in cognitively unimpaired carriers of the presenilin-1 (PSEN1) E280A mutation for autosomal dominant AD. Methods: A total of 27 PSEN1 mutation carriers and 26 non-carrier family members were included. Linear regression was used to test the relationship between hippocampal volume and 15-item Geriatric Depression Scale. Results: Carriers and non-carriers did not differ in depressive symptoms or hippocampal volume. Within carriers, lower hippocampal volume was associated with greater depressive symptoms, which remained significant after adjusting for age and cognition. This relationship was not significant in non-carriers. Discussion: Hippocampal neurodegeneration may underlie depressive symptoms in preclinical autosomal dominant AD. These findings provide support for the utility of targeting depressive symptoms in AD prevention. Highlights: We compared unimpaired autosomal dominant Alzheimer's disease (AD) mutation carriers and non-carriers. Carriers and non-carriers did not differ in severity of depressive symptoms. In carriers, hippocampal volume was inversely associated with depressive symptoms. Depressive symptoms may be a useful target in AD prevention.
MeSH term(s)	Humans ; Aged ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/genetics ; Alzheimer Disease/complications ; Depression/genetics ; Mutation/genetics ; Hippocampus/diagnostic imaging ; Presenilin-1/genetics ; Cognition
Chemical Substances	Presenilin-1
Language	English
Publishing date	2023-10-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13501
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Zs.A 6316: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 540: Show issues

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Article ; Online: Measurement of Cerebral Perfusion Indices from the Early Phase of [

Guehl, Nicolas J / Dhaynaut, Maeva / Hanseeuw, Bernard J / Moon, Sung-Hyun / Lois, Cristina / Thibault, Emma / Fu, Jessie Fanglu / Price, Julie C / Johnson, Keith A / El Fakhri, Georges / Normandin, Marc D

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2023 Volume 64, Issue 6, Page(s) 968–975

Abstract: 6-(fluoro- ...

Abstract	6-(fluoro-
MeSH term(s)	Humans ; Alzheimer Disease/diagnostic imaging ; Brain/diagnostic imaging ; Positron-Emission Tomography/methods ; Cognitive Dysfunction/diagnostic imaging ; Aniline Compounds ; Cerebrovascular Circulation
Chemical Substances	Aniline Compounds
Language	English
Publishing date	2023-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.122.265072
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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Contribution of extracerebral tracer retention and partial volume effects to sex differences in Flortaucipir-PET signal.

Scott, Matthew R / Edwards, Natalie C / Properzi, Michael J / Jacobs, Heidi Il / Price, Julie C / Lois, Cristina / Farrell, Michelle E / Hanseeuw, Bernard J / Thibault, Emma G / Rentz, Dorene M / Johnson, Keith A / Sperling, Reisa A / Schultz, Aaron P / Buckley, Rachel F

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

2023 Volume 44, Issue 1, Page(s) 131–141

Abstract: Clinically normal females exhibit ... ...

Abstract	Clinically normal females exhibit higher
MeSH term(s)	Humans ; Male ; Female ; tau Proteins/metabolism ; Brain/diagnostic imaging ; Brain/metabolism ; Sex Characteristics ; Cross-Sectional Studies ; Positron-Emission Tomography/methods ; Carbolines/metabolism ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/metabolism ; Alzheimer Disease/metabolism
Chemical Substances	7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole (J09QS3Z3WB) ; tau Proteins ; Carbolines
Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604628-9
ISSN	1559-7016 ; 0271-678X
ISSN (online)	1559-7016
ISSN	0271-678X
DOI	10.1177/0271678X231196978
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Article ; Online: Association of Emerging β-Amyloid and Tau Pathology With Early Cognitive Changes in Clinically Normal Older Adults.

Farrell, Michelle E / Papp, Kathryn V / Buckley, Rachel F / Jacobs, Heidi I L / Schultz, Aaron P / Properzi, Michael J / Vannini, Patrizia / Hanseeuw, Bernard J / Rentz, Dorene M / Johnson, Keith A / Sperling, Reisa A

Neurology

2022 Volume 98, Issue 15, Page(s) e1512–e1524

Abstract: Background and objectives: Alzheimer disease (AD) clinical trials are moving earlier in the disease process according to emerging signs of β-amyloid (Aβ) and tau pathology. If early treatment is the right time for intervention, it is critical to find ... ...

Abstract	Background and objectives: Alzheimer disease (AD) clinical trials are moving earlier in the disease process according to emerging signs of β-amyloid (Aβ) and tau pathology. If early treatment is the right time for intervention, it is critical to find the right test to optimize cognitive outcome measures for clinical trials. We sought to identify cognitive measures associated with the earliest detectable signs of emerging Aβ and tau pathology. Methods: One hundred twelve clinically normal adults with longitudinal Pittsburgh compound B (PiB)-PET, Results: Steeper PiB slopes were associated with declining processing speed (Digit Symbol Substitution Test [DSST], Trail Making Test Part A) in those <CL20 and expanded to include learning/memory retrieval (FCSRT-FR], Selective Reminding Test Total Recall [SRT-tr], Logical Memory Immediate Recall) in the <CL40 group. FTP had limited effects under CL20, with only rising right IT FTP slope related to declining FCSRT-FR and SRT-tr learning/memory retrieval. When we expanded to include those initially <CL40, rising FTP level or slope was related to declines across all tasks, and PiB slope effects on memory retrieval but not DSST score were reduced. A composite measure of processing speed and memory retrieval tasks provided the strongest prediction of decline under CL40, while PACC score remained optimal at high levels of Aβ (>CL40). Discussion: Early, Aβ-mediated cognitive slowing was detected for processing speed measures, while early memory retrieval declines were associated with emerging Aβ and tau pathology. Composites of these measures may help determine whether anti-Aβ or anti-tau therapies administered at the first signs of pathology might preserve cognitive function. Classification of evidence: This study provides Class I evidence that in clinically normal older adults, emerging PET-detected AD pathology is associated with declining processing speeds and memory retrieval.
MeSH term(s)	Aged ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Brain/pathology ; Cognition ; Cognitive Dysfunction/pathology ; Humans ; Positron-Emission Tomography ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; MAPT protein, human ; tau Proteins
Language	English
Publishing date	2022-03-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000200137
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Article ; Online: Associations Between Brainstem Volume and Alzheimer's Disease Pathology in Middle-Aged Individuals of the Framingham Heart Study.

Jacobs, Heidi I L / O'Donnell, Adrienne / Satizabal, Claudia L / Lois, Cristina / Kojis, Daniel / Hanseeuw, Bernard J / Thibault, Emma / Sanchez, Justin S / Buckley, Rachel F / Yang, Qiong / DeCarli, Charles / Killiany, Ron / Sargurupremraj, Muralidharan / Sperling, Reisa A / Johnson, Keith A / Beiser, Alexa S / Seshadri, Sudha

Journal of Alzheimer's disease : JAD

2022 Volume 86, Issue 4, Page(s) 1603–1609

Abstract: The brainstem is among the first regions to accumulate Alzheimer's disease (AD)-related hyperphosphorylated tau pathology during aging. We aimed to examine associations between brainstem volume and neocortical amyloid-β or tau pathology in 271 middle- ... ...

Abstract	The brainstem is among the first regions to accumulate Alzheimer's disease (AD)-related hyperphosphorylated tau pathology during aging. We aimed to examine associations between brainstem volume and neocortical amyloid-β or tau pathology in 271 middle-aged clinically normal individuals of the Framingham Heart Study who underwent MRI and PET imaging. Lower volume of the medulla, pons, or midbrain was associated with greater neocortical amyloid burden. No associations were detected between brainstem volumes and tau deposition. Our results support the hypothesis that lower brainstem volumes are associated with initial AD-related processes and may signal preclinical AD pathology.
MeSH term(s)	Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Brain Stem/pathology ; Humans ; Longitudinal Studies ; Middle Aged ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; tau Proteins
Language	English
Publishing date	2022-02-25
Publishing country	Netherlands
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-215372
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Article ; Online: Evolution of anosognosia in alzheimer's disease and its relationship to amyloid.

Hanseeuw, Bernard J / Scott, Matthew R / Sikkes, Sietske A M / Properzi, Michael / Gatchel, Jennifer R / Salmon, Eric / Marshall, Gad A / Vannini, Patrizia

Annals of neurology

2019 Volume 87, Issue 2, Page(s) 267–280

Abstract: Objective: Unawareness, or anosognosia, of memory deficits is a challenging manifestation of Alzheimer's disease (AD) that adversely affects a patient's safety and decision-making. However, there is a lack of consensus regarding the presence, as well as ...

Abstract	Objective: Unawareness, or anosognosia, of memory deficits is a challenging manifestation of Alzheimer's disease (AD) that adversely affects a patient's safety and decision-making. However, there is a lack of consensus regarding the presence, as well as the evolution, of altered awareness of memory function across the preclinical and prodromal stages of AD. Here, we aimed to characterize change in awareness of memory abilities and its relationship to beta-amyloid (Aβ) burden in a large cohort (N = 1,070) of individuals across the disease spectrum. Methods: Memory awareness was longitudinally assessed (average number of visits = 4.3) and operationalized using the discrepancy between mean participant and partner report on the Everyday Cognition scale (memory domain). Aβ deposition was measured at baseline using [18F]florbetapir positron emission tomographic imaging. Results: Aβ predicted longitudinal changes in memory awareness, such that awareness decreased faster in participants with increased Aβ burden. Aβ and clinical group interacted to predict change in memory awareness, demonstrating the strongest effect in dementia participants, but could also be found in the cognitively normal (CN) participants. In a subset of CN participants who progressed to mild cognitive impairment (MCI), heightened memory awareness was observed up to 1.6 years before MCI diagnosis, with memory awareness declining until the time of progression to MCI (-0.08 discrepant-points/yr). In a subset of MCI participants who progressed to dementia, awareness was low initially and continued to decline (-0.23 discrepant-points/yr), reaching anosognosia 3.2 years before dementia onset. Interpretation: Aβ burden is associated with a progressive decrease in self-awareness of memory deficits, reaching anosognosia approximately 3 years before dementia diagnosis. ANN NEUROL 2020;87:267-280.
MeSH term(s)	Aged ; Agnosia/complications ; Agnosia/metabolism ; Agnosia/psychology ; Alzheimer Disease/complications ; Alzheimer Disease/metabolism ; Alzheimer Disease/psychology ; Amyloid beta-Peptides/metabolism ; Brain/metabolism ; Disease Progression ; Female ; Functional Neuroimaging ; Humans ; Male ; Memory Disorders/complications ; Neuropsychological Tests ; Positron-Emission Tomography ; Prodromal Symptoms ; Prospective Studies
Chemical Substances	Amyloid beta-Peptides
Language	English
Publishing date	2019-12-05
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.25649
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