Alzheimer's Disease: Neuropathologic Findings and Recent Advances in Imaging

HOME

HELP

FEEDBACK

SUBSCRIPTIONS

Alzheimer's Disease: Neuropathologic Findings and Recent Advances in Imaging

Joseph F. Norfray¹ and James M. Provenzale²

¹ Chicago Northside MRI Center, 2818 N Sheridan Rd., Chicago, IL 60657.
² Department of Radiology, Duke University Medical Center, Durham, NC 27710.

View larger version (21K):

[in a new window]

Fig. 1. —Schematic drawing shows origin of protein fragments. Amyloid precursor protein (APP) is neuronal cell membrane surface receptor and is source of amyloid and nonamyloid protein fragments. Both fragments are released from surface receptor by different enzymatic secretases ( ${alpha}$ , ß, ${gamma}$ ). Activated amyloid B protein (ABP) forms amyloid. Activated APP soluble (APPs) increases length and branching of axons and dendrites. Both fragments contain binding sites (BS) that activate fragments. Heparin sulfate (HS) bonds to both ABP and APPs; nerve growth factor (NGF) bonds to APPs.

View larger version (10K):

[in a new window]

Fig. 2. —Schematic drawing shows formation of amyloid. Activation of amyloid B protein (ABP) binding site by nidus bonds heparin sulfate of carbohydrate (GAGs), causing aggregation of individual APB fragments into beta sheet amyloid.

View larger version (8K):

[in a new window]

Fig. 3. —Schematic drawing shows formation of neurofibrillary tangles (NFT). Tau, protein of microtubules, forms NFT when hyperphosphorylated by enzyme microtubule affinity regulating kinase (MARK). MARK is coupled to inositol signaling pathway (ISP).

View larger version (87K):

[in a new window]

Fig. 4A. —Measurement of hippocampal volumes using T1-weighted 3D spoiled gradient-recalled echo sequence in 75-year-old woman at time of diagnosis of mild cognitive impairment. This patient's cognitive status remained stable during 49-month follow-up period. (Reprinted with permission from [28]) Unenhanced coronal T1-weighted image shows relatively normal volume in body of hippocampus. Boundary used for hippocampal measurement is outlined in white.

View larger version (85K):

[in a new window]

Fig. 4B. —Measurement of hippocampal volumes using T1-weighted 3D spoiled gradient-recalled echo sequence in 75-year-old woman at time of diagnosis of mild cognitive impairment. This patient's cognitive status remained stable during 49-month follow-up period. (Reprinted with permission from [28]) Unenhanced coronal T1-weighted image at region more anterior than that shown in A also shows relatively normal volume in head of hippocampus. Boundary used for hippocampal measurement is outlined in white.

View larger version (84K):

[in a new window]

Fig. 5A. —Measurement of hippocampal volumes using T1-weighted 3D spoiled gradient-recalled echo sequence in 70-year-old woman at time of initial diagnosis of mild cognitive impairment. This patient progressed to dementia over 43-month follow-up period. Comparison of these images with those shown in Figure 4A, 4B shows possible use of volumetric imaging to predict subsequent course. (Reprinted with permission from [28]) Unenhanced coronal T1-weighted image shows relatively decreased volume in body of hippocampus. Boundary used for hippocampal measurement is outlined in white. Note that compared with patient shown in Figure 4A, hippocampal volume is decreased even though this patient is 5 years younger than patient shown in Figure 4A, 4B.

View larger version (80K):

[in a new window]

Fig. 5B. —Measurement of hippocampal volumes using T1-weighted 3D spoiled gradient-recalled echo sequence in 70-year-old woman at time of initial diagnosis of mild cognitive impairment. This patient progressed to dementia over 43-month follow-up period. Comparison of these images with those shown in Figure 4A, 4B shows possible use of volumetric imaging to predict subsequent course. (Reprinted with permission from [28]) Unenhanced coronal T1-weighted image at region more anterior than that shown in A also shows decreased volume in head of hippocampus. Boundary used for hippocampal measurement is outlined in white. Again, size of hippocampus in this patient is decreased compared with patient who did not progress to dementia, as shown in Figure 4B.

View larger version (144K):

[in a new window]

Fig. 6. —Potential role of cerebral blood volume images for aiding in diagnosis of Alzheimer's disease. Cerebral blood volume map obtained using T2*-weighted perfusion imaging is shown in 83-year-old woman with probable Alzheimer's disease and Mini-Mental State Examination score of 11 (normal, $>=$ 27.6). Cerebral blood volume in temporoparietal regions (outlined in white) measured approximately 65% of reference cerebral blood volume in cerebellum in this patient (compared with mean of 112% in healthy control subjects), indicating diminished cerebral blood volume in same regions that are generally seen in Alzheimer's disease patients studied with positron emission tomography and SPECT. (Reprinted with permission from [50])

View larger version (20K):

[in a new window]

Fig. 7. —Plot shows comparison of ratio of relative cerebral blood volume measurements in temporoparietal regions to relative cerebral blood volume measurements in cerebellar cortex (x-axis) with Mini-Mental State Examination (MMSE) scores (y-axis) in patients with possible or probable Alzheimer's disease. Comparison shows that, as level of cognitive functioning decreases, relative cerebral blood volume measurements in these brain regions also tend to decrease. Note that although distinct separation between relative cerebral blood volume in patients with normal scores and those with lowered scores is not seen, clear trend toward lower relative cerebral blood volume in subjects with lower scores is evident. (Courtesy of Renshaw P, Belmont, MA)

View larger version (112K):

[in a new window]

Fig. 8A. —Differences in sites and sizes of regions of brain activation after memory task of patient with mild cognitive impairment and control subject. 67-year-old man shown in B was one of group of subjects with mild cognitive impairment who were found to have statistically less activation than control subjects in five of seven brain regions studied; similar trend that was not statistically significant was seen in other two brain regions. Brain activation studies in both groups were obtained in identical fashion and were analyzed using same statistical threshold, smoothing and clustering. (Courtesy of Petrella J, Durham, NC) Brain activation functional imaging performed during memory task in 71-year-old man with normal cognitive functioning, on no medication, shows robust activation (depicted in colored voxels) in right frontal lobe.

View larger version (119K):

[in a new window]

Fig. 8B. —Differences in sites and sizes of regions of brain activation after memory task of patient with mild cognitive impairment and control subject. 67-year-old man shown in B was one of group of subjects with mild cognitive impairment who were found to have statistically less activation than control subjects in five of seven brain regions studied; similar trend that was not statistically significant was seen in other two brain regions. Brain activation studies in both groups were obtained in identical fashion and were analyzed using same statistical threshold, smoothing and clustering. (Courtesy of Petrella J, Durham, NC) Brain activation functional imaging performed during memory task in 67-year-old man with mild cognitive impairment (receiving no medication) shows decreased activation (depicted in color voxel overlay) in right frontal lobe compared with individual shown in A. Note activation in left frontal lobe, which suggests possible contralateral hemisphere compensatory activation.

View larger version (63K):

[in a new window]

Fig. 9A. —MR spectroscopic findings in 78-year-old woman with probable Alzheimer's disease. Coronal T2-weighted fast spin-echo image shows severe cortical atrophy in both hippocampi.

View larger version (134K):

[in a new window]

Fig. 9B. —MR spectroscopic findings in 78-year-old woman with probable Alzheimer's disease. Axial T2-weighted spin-echo image (stimulated echo acquisition mode, TR/TE, 1,500/30; average of 128 scans; mixing time, 13.7 msec) shows bitemporal volume loss. Voxel for MR spectroscopy has been drawn on parietal lobe and posterior cingulate gyrus.

View larger version (14K):

[in a new window]

Fig. 9C. —MR spectroscopic findings in 78-year-old woman with probable Alzheimer's disease. Spectrum from voxel depicted in B shows decreased N-acetylaspartate (NAA) levels, with NAA-to-creatine (CRE) ratio of 1.13, indicating neuronal loss. Elevated myo-inositol (MI) levels, with MI-to-creatine ratio of 0.70, are consistent with gliosis. CHO = choline.

View larger version (11K):

[in a new window]

Fig. 10. —Spectra from posterior cingulate cortex (point resolved spectroscopy, TR/TE, 2,000/30; average of 128 scans) obtained from control subject (top row), patient with mild cognitive impairment (MCI, middle row), and patient with probable Alzheimer's disease (AD, bottom row). Myo-inositol (MI) to creatine (Cr) ratios show progressive increase in mild cognitive impairment (0.65) and Alzheimer's disease (0.81) compared with control subject (0.48). Note also significant reduction in N-acetylaspartate (NAA) to creatine (Cr) ratios in Alzheimer's disease subject (1.33) compared with patient with mild cognitive impairment (1.60) and control subject (1.71). CHO = choline. (Reprinted with permission from [64])

CiteULike

Complore

Connotea

Del.icio.us Add to Digg

Digg

Technorati What's this?