70 μm sections were independently examined by experienced
investigators (JB, DJI) and graded on a standard validated ordinal scale (i.e.
0=none/rare, 1=mild, 2=moderate,
3=severe)10 (link), 15 (link), 25 (link) for the burden of tau deposition and neuronal loss in
the following regions: amygdala (AMY), hippocampus (HIPP), orbitofrontal cortex
(OFC), mid-frontal cortex (MFC), anterior cingulate gyrus (ACG),
superior/mid-temporal gyri (SMT), primary motor cortex (MOT), angular gyrus
(ANG), primary sensory cortex (SENS), primary visual cortex (VIS), caudate
nucleus and putamen (striatum STR), globus pallidus (GP), thalamus (THAL),
midbrain, pons, medulla (MED), cerebellum (CB) and cervical spinal cord (CSC).
Anatomic regions/nuclei within these sections examined included: the cornu
ammonis/subiculum (CA), entorhinal cortex (ERC) and dentate gyrus (DG) in HIPP;
substantia nigra (MBSN) and red nucleus (MBRN) in midbrain; locus coeruleus (LC)
and raphe nuclei (RPN) in the pons; hypoglossal nucleus (MEDXII), dorsal motor
nucleus of the vagus (MEDX), reticular formation (MEDRF), inferior olive
(MEDIO), and arcuate nucleus and pontobulbar body pre-cerebellar nuclei (MED
ARC/PB); dentate nucleus (CBDG) and granular layer (CBGL) of the cerebellum.
Discrepant scores were re-reviewed by both examiners and consensus scores were
reached. Sections were also separately graded for the severity of ramified
astrocytes and tau pathology in adjacent white matter (WM). Finally, since PiD
can preferentially affect specific cortical lamina (i.e. II, VI) 26 , cortical sections were also
examined for tau deposition in superficial cortical layers (layers II-III) and
deep cortical layers (V-VI). Hypothetical phases of sequential tau deposition
were constructed through comparison of regional involvement for AT-8 staining in
70 μm thick sections.
A subset of regions (AMY, ERC, DG, CA, MFC, OFC, ACG, SMT, ANG, SENS,
STR, MOT, VIS) were selected for 6 μm section IHC experiments for UBQ,
ThS, Tau C3, RD4 and anti-4R tau and graded on a similar ordinal scale.
investigators (JB, DJI) and graded on a standard validated ordinal scale (i.e.
0=none/rare, 1=mild, 2=moderate,
3=severe)10 (link), 15 (link), 25 (link) for the burden of tau deposition and neuronal loss in
the following regions: amygdala (AMY), hippocampus (HIPP), orbitofrontal cortex
(OFC), mid-frontal cortex (MFC), anterior cingulate gyrus (ACG),
superior/mid-temporal gyri (SMT), primary motor cortex (MOT), angular gyrus
(ANG), primary sensory cortex (SENS), primary visual cortex (VIS), caudate
nucleus and putamen (striatum STR), globus pallidus (GP), thalamus (THAL),
midbrain, pons, medulla (MED), cerebellum (CB) and cervical spinal cord (CSC).
Anatomic regions/nuclei within these sections examined included: the cornu
ammonis/subiculum (CA), entorhinal cortex (ERC) and dentate gyrus (DG) in HIPP;
substantia nigra (MBSN) and red nucleus (MBRN) in midbrain; locus coeruleus (LC)
and raphe nuclei (RPN) in the pons; hypoglossal nucleus (MEDXII), dorsal motor
nucleus of the vagus (MEDX), reticular formation (MEDRF), inferior olive
(MEDIO), and arcuate nucleus and pontobulbar body pre-cerebellar nuclei (MED
ARC/PB); dentate nucleus (CBDG) and granular layer (CBGL) of the cerebellum.
Discrepant scores were re-reviewed by both examiners and consensus scores were
reached. Sections were also separately graded for the severity of ramified
astrocytes and tau pathology in adjacent white matter (WM). Finally, since PiD
can preferentially affect specific cortical lamina (i.e. II, VI) 26 , cortical sections were also
examined for tau deposition in superficial cortical layers (layers II-III) and
deep cortical layers (V-VI). Hypothetical phases of sequential tau deposition
were constructed through comparison of regional involvement for AT-8 staining in
70 μm thick sections.
A subset of regions (AMY, ERC, DG, CA, MFC, OFC, ACG, SMT, ANG, SENS,
STR, MOT, VIS) were selected for 6 μm section IHC experiments for UBQ,
ThS, Tau C3, RD4 and anti-4R tau and graded on a similar ordinal scale.
