Page 97 - MEGIN Book Of Abstracts - 2023

BACKGROUND The mechanism of synaptic loss in Cortical connectivity of the nucleus basalis of
Alzheimer's disease is poorly understood and may be Meynert in Parkinson's disease and Lewy body
associated with tau pathology. In this combined posi- dementias (2021)
tron emission tomography (PET) and magnetoenceph-
alography (MEG) study, we aimed to investigate spatial Oswal, Ashwini; Gratwicke, James; Akram, Harith;
associations between regional tau pathology ([[18] Jahanshahi, Marjan; Zaborszky, Laszlo; Brown, Peter;
F]flortaucipir PET), synaptic density (synaptic vesicle Hariz, Marwan; Zrinzo, Ludvic; Foltynie, Tom; Litvak,
2A [[11]C]UCB-J PET) and synaptic function (MEG) in Vladimir
Alzheimer's disease.
Wellcome Centre for Human Neuroimaging, UCL Institute of
METHODS Seven amyloid-positive Alzheimer's disease Neurology, London, UK; Department of Clinical and Move-
subjects from the Amsterdam Dementia Cohort under- ment Neurosciences, UCL Institute of Neurology and The
went dynamic 130-min [[18]F]flortaucipir PET, dynamic National Hospital for Neurology and Neurosurgery, Queen
60-min [[11]C]UCB-J PET with arterial sampling and Square, London, UK; Center for Molecular and Behavioral
2 × 5-min resting-state MEG measurement. [[18]F] Neuroscience, Rutgers University, Newark, USA; Nuffield De-
flortaucipir- and [[11]C]UCB-J-specific binding (binding partment of Clinical Neurosciences, John Radcliffe Hospital,
potential, BPND) and MEG spectral measures (relative Oxford, UK; Department of Clinical Neuroscience, Umeå
delta, theta and alpha power; broadband power; and University, Umeå, Sweden
peak frequency) were assessed in cortical brain re-
gions of interest. Associations between regional [[18]F] ABSTRACT Parkinson's disease dementia (PDD) and
flortaucipir BPND, [[11]C]UCB-J BPND and MEG spectral dementia with Lewy bodies (DLB) are related condi-
measures were assessed using Spearman correlations tions that are associated with cholinergic system dys-
and generalized estimating equation models. function. Dysfunction of the nucleus basalis of Meynert
(NBM), a basal forebrain structure that provides the
RESULTS Across subjects, higher regional [[18]F]flor- dominant source of cortical cholinergic innervation,
taucipir uptake was associated with lower [[11]C]UCB-J has been implicated in the pathogenesis of both PDD
uptake. Within subjects, the association between [[11] and DLB. Here we leverage the temporal resolution
C]UCB-J and [[18]F]flortaucipir depended on within- of magnetoencephalography with the spatial resolu-
subject neocortical tau load; negative associations were tion of MRI tractography to explore the intersection of
observed when neocortical tau load was high, gradu- functional and structural connectivity of the NBM in a
ally changing into opposite patterns with decreasing unique cohort of PDD and DLB patients undergoing
neocortical tau burden. Both higher [[18]F]flortaucipir deep brain stimulation of this structure. We observe
and lower [[11]C]UCB-J uptake were associated with that NBM-cortical structural and functional connectiv-
altered synaptic function, indicative of slowing of oscil- ity correlate within spatially and spectrally segregated
latory activity, most pronounced in the occipital lobe. networks including: (i) a beta band network to supple-
mentary motor area, where activity in this region was
CONCLUSIONS These results indicate that in Alzheim- found to drive activity in the NBM; (ii) a delta/theta
er's disease, tau pathology is closely associated with band network to medial temporal lobe structures
reduced synaptic density and synaptic dysfunction. encompassing the parahippocampal gyrus; and (iii)
a delta/theta band network to visual areas including
Keywords: Alzheimer, MEG, PET, Synaptic density, Synaptic lingual gyrus. These findings reveal functional net-
function, Tau works of the NBM that are likely to subserve important
roles in motor control, memory and visual function,
Alzheimer's research & therapy (2021), Vol. 13, No. 1 respectively. Furthermore, they motivate future studies
(33546722) (24 citations) aimed at disentangling network contribution to disease
phenotype.

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